Ekspresi Endotelin-1 pada Berbagai Variasi Histopatologis Keratosis Seboroik
EKSPRESI ENDOTELIN-1 PADA BERBAGAI VARIASI
HISTOPATOLOGIS KERATOSIS SEBOROIK
TESIS
Oleh
dr. EVITA LOURDES PINEM
PROGRAM PENDIDIKAN DOKTER SPESIALIS
DEPARTEMEN ILMU KESEHATAN KULIT DAN KELAMIN
FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA
MEDAN
2017
Universitas Sumatera Utara
Ekspresi Endotelin-1 pada Berbagai Variasi Histopatologis Keratosis Seboroik
Evita Lourdes Pinem, Imam Budi Putra, Nelva Karmila Jusuf
Departemen Ilmu Kesehatan Kulit dan Kelamin
Fakultas Kedokteran Universitas Sumatera Utara
RSUP H. Adam Malik Medan
Abstrak:
Latar belakang: Keratosis seboroik adalah suatu tumor benigna yang terdiri dari keratinosit
epidermis dengan pigmentasi meningkat. Variasi histopatologis keratosis seboroik adalah:
akantotik, flat, irritated, stuccokeratosis, pigmented, reticulated, pedunculated, dermatosis
papulose nigra, dan klonal. Diduga bahwa melanisasi yang meningkat yang terobservasi pada
keratosis seboroik dikaitkan dengan produksi endotelin-1 yang meningkat pada proliferasi
keratinosit yang tinggi sehingga menimbulkan neoplasma.
Tujuan: Mengetahui ekspresi endotelin-1 pada berbagai variasi histopatologis keratosis
seboroik.
Metode: Penelitian ini menggunakan studi deskriptif observasional laboratoris dengan
rancangan potong lintang yang menggunakan 40 blok parafin yang telah diperiksa secara
histopatologis sebagai keratosis seboroik dan telah ditentukan variasi histopatologinya.
Hasil: Ekspresi endotelin-1 pada 14 sampel keratosis seboroik varian akantotik didapati kuat
4 sampel (28,57%), sedang 4 sampel (28,57%), dan lemah 6 sampel (42,85%), dan letak
endotelin-1 pada stratum basalis 9 sampel (64,28%), 1/3 bawah lapisan epidermis 1 sampel
(7,14%), dan seluruh lapisan epidermis 4 sampel (28,57%). Ekspresi endotelin-1 pada 6
sampel keratosis seboroik varian flat didapati kuat 1 sampel (16,67 %), sedang 2 sampel
(33,33%), dan lemah 3 sampel (50 %) dan letak endotelin-1 pada stratum basalis 5 sampel
(83,33%), dan 1/3 bawah lapisan epidermis 1 sampel (16,66%). Ekspresi endotelin-1 pada1
sampel keratosis seboroik varian irritated didapati lemah 1 sampel (100%) dan letak
endotelin-1 pada seluruh lapisan epidermis 1 sampel (100%). Ekspresi endotelin-1 pada 6
sampel keratosis seboroik varian stuccokeratosis didapati kuat pada 2 sampel (33,33 %),
sedang 1 sampel (16,67%), dan lemah 3 sampel (50%) dan letak endotelin-1 pada stratum
basalis 4 sampel (66,67%), 1/3 bawah lapisan epidermis 1 sampel (16,66%), dan seluruh
lapisan epidermis 1 sampel (16,66%). Ekspresi endotelin-1 pada 2 sampel keratosis seboroik
varian pigmented didapati kuat pada 2 sampel (100 %) dan letak endotelin-1 pada stratum
basalis 1 sampel (50%), dan seluruh lapisan epidermis 1 sampel (50%). Ekspresi endotelin-1
pada 7 sampel keratosis seboroik varian reticulated didapati kuat 1 sampel (14,28%), sedang
4 sampel (57,14%), dan lemah 2 sampel (28,57%) dan letak endotelin-1 pada stratum basalis
7 sampel (100%). Ekspresi endotelin-1 pada 1 sampel keratosis seboroik varian pedunculated
didapati sedang 1 sampel (100%) dan letak endotelin-1 pada lapisan stratum basalis 1 sampel
(100%). Ekspresi endotelin-1 pada 3 sampel keratosis seboroik varian dermatosis papulose
nigra didapati sedang 2 sampel (66,67%), dan lemah 1 sampel (33,33%) dan letak
endotelin-1 pada stratum basalis 2 sampel (66,67%), dan seluruh lapisan epidermis 1 sampel
(33,33%).
Kesimpulan: Dilihat dari ekspresi endotelin-1 pada berbagai variasi histopatologis keratosis
seboroik maka didapatkan ekspresi endotelin-1 yang kuat 25% (tipe akantotik 10%,
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stuccokeratosis 5%, pigmented 5%, flat 2,5%, dan reticulated 2,5%), sedang 35% (akantotik
10%, flat 5%, stuccokeratosis 2,5%, reticulated 10%, pedunculated 2,5%, dermatosis
papulose nigra 5%), dan lemah 40% (akantotik 15%, flat 7,5%, irritated 2,5%,
stuccokeratosis 7,5%, reticulated/ adenoid 5%, dan 1 dermatosis papulose nigra 2,5%).
Kata kunci: Keratosis seboroik, ekspresi endotelin-1.
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Endothelin-1 Expressions on Seborrheic Keratosis Histopathology Variants
Evita Lourdes Pinem, Imam Budi Putra, Nelva Karmila Jusuf
Dermatovenereology Department
University of Sumatera Utara Medical Faculty
H. Adam Malik Centre General Hospital Medan
Abstract
Background: Seborrheic keratosis is a benign tumor, composed of keratynocites with
increased pigmentation. Seborrheic keratosis histopathological variants are acanthotic, flat,
irritated, stuccokeratosis, pigmented, reticulated, pedunculated, dermatosis papulose nigra,
and klonal. It suggested that the enhanced pigmentation in seborrheic keratosis is attributable
to the upregulated expression of endothelin-1 by highly proliferating basaloid cells.
Objective: To describe endothelin-1 expression on seborrheic keratosis histopathological
variants.
Materials and Methods: This study was descriptive observasional and cross sectional study,
used 40 samples of seborrheic keratosis’ lesions that diagnosed based on histopathological
examinations, and the histopathological variants have determined.
Result: Endothelin-1 expressions of 14 acanthotic variants were strong 4 samples (28,57%),
moderate 4 samples (28,57%), and weak 6 samples (42,85%) and endothelin-1 was located
in stratum basale 9 samples (64,28%), one-third lower part of the epidermis 1 sample
(7,14%), and epidermis 4 samples (28,57%). Endothelin-1 expressions of 6 flat variants were
strong 1 sample (16,67%), moderate 2 samples (33,33%), and weak 3 samples (50%) and
endothelin-1 was located in stratum basale 5 samples (83,33%) and one-third lower part of
the epidermis 1 sample (16,66%). Endothelin-1 expression of 1 irritated variant was weak 1
sample (100%) and endothelin-1 was located in epidermis 1 sample (100 %). Endothelin-1
expressions of 3 stuccokeratosis variants were strong 2 samples (33,33%), moderate 1
sample (16,67%), and weak 3 samples (50%) and endothelin-1 was located in stratum basale
4 samples (66,67%), one-third lower part of the epidermis 1 sample (16,66%), and epidermis
1 sample (16,66%). Endothelin-1 expressions of 2 pigmented variants were strong 2 (10%)
and endothelin-1 was located in stratum basale 1 sample (50%), and epidermis 1 sampel
(50%). Endothelin-1 expressions of 7 reticulated variants were strong 1 sampel (14,28%),
moderate 4 samples (57,14%), and weak 2 samples (28,57%) and endothelin-1 was located in
stratum basale 7 samples(100%). Endothelin-1 expression of 1 pedunculated variant was
moderate 1 sample (100%) and endothelin-1 was located in stratum basale 1 sample (100%).
Endothelin-1 expressions of 3 dermatosis papulose nigra variants were moderate 2 samples
(66,67%) and weak 1 sample (33,33%) and endothelin-1 was located in stratum basale 2
samples (66,67%) and epidermis 1 sample (33,33%).
Conclusion: Endothelin-1 expressions of seborrheic keratosis histopathological variants were
strong 25% (acanthotic 10 %, stuccokeratosis 5%, pigmented 5%, flat 2,5%, and reticulated
2,5%), moderate 35% (acanthotic 10%, flat 5%, stuccokeratosis 2,5%, reticulated 10%,
pedunculated 2,5%, dermatosis papulose nigra 5%), and weak 40% (acanthotic 15%, flat
7,5%, irritated 2,5%, stuccokeratosis 7,5%, reticulated/adenoid 5% and dermatosis papulose
nigra 2,5%).
Key words: seborrheic keratosis, endothelin-1 expression.
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DAFTAR ISI
Halaman
ABSTRAK ................................................................................................................ i
ABSTRACT ........................................................................................................... iii
DAFTAR ISI ........................................................................................................... iv
DAFTAR SINGKATAN ....................................................................................... vi
DAFTAR TABEL..................................................................................................vii
DAFTAR GAMBAR ........................................................................................... viii
DAFTAR LAMPIRAN ........................................................................................... ix
BAB I
PENDAHULUAN ................................................................................ 1
1.1 Latar Belakang ............................................................................ 1
1.2 Rumusan Masalah........................................................................ 3
1.3 Tujuan Penelitian ......................................................................... 3
1.3.1 Tujuan umum...................................................................... 3
1.3.2 Tujuan khusus ..................................................................... 3
1.4 Manfaat penelitian ....................................................................... 5
1.4.1. Akademik........................................................................... 5
1.4.2. Penelitian ........................................................................... 5
BAB II
TINJAUAN PUSTAKA ....................................................................... 6
2.1 Keratosis Seboroik ....................................................................... 6
2.1.1. Epidemiologi .................................................................... 6
2.1.2. Etiopatogenesis ................................................................ 7
2.1.3. Faktor risiko ..................................................................... 9
2.1.4. Gambaran klinis.............................................................. 10
2.1.5. Diagnosis banding ......................................................... 11
2.1.6. Diagnosis ........................................................................ 12
2.1.7 Variasi histopatologis ..................................................... 12
2.1.8. Penatalaksanaan .............................................................. 18
2.1.9. Prognosis ........................................................................ 21
2.2 Endotelin-1 ................................................................................ 21
2.3 Fungsi Endotelin-1 .................................................................... 21
2.4 Peran Endotelin-1 pada Keratosis Seboroik.............................. 22
2.5 Kerangka Teori ......................................................................... 26
2.6 Kerangka Konsep ..................................................................... 27
BAB III
METODE PENELITIAN .................................................................... 28
3.1 Desain Penelitian ....................................................................... 28
3.2 Waktu dan Tempat Penelitian.................................................... 28
3.3 Sampel Penelitian ...................................................................... 28
3.4 Besar Sampel ............................................................................. 29
3.5 Cara Pengambilan Sampel penelitian ........................................ 30
3.6 Definisi Operasional .................................................................. 30
3.7 Alat, Bahan dan Cara Kerja ....................................................... 32
3.7.1 Alat… ........................................ …………………………32
3.7.2 Bahan… ................................. ……………………………32
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3.7.3 Cara kerja… .......................... ……………………………33
3. 8 Kerangka Operasional ................................................................ 35
3. 9 Ethical Clearance ...................................................................... 35
BAB IV
HASIL PENELITIAN DAN PEMBAHASAN .................................. 36
4.1 Variasi Histopatologis ............................................................... 36
4.2 Hasil Pemeriksaan Imunohistokimia ........................................ 37
4.2.1 Ekspresi endotelin-1 berdasarkan
variasi histopatologis- nya ............................................... 37
4.2.2 Letak endotelin-1 ............................................................. 42
4.2.3 Ekspresi dan letak endotelin-1 berdasarkan variasi ..............
histopatologisnya .............................................................. 44
BAB V
KESIMPULAN DAN SARAN ........................................................... 47
5.1 Kesimpulan ................................................................................ 47
5.1 Saran .......................................................................................... 48
DAFTAR PUSTAKA ............................................................................................ 49
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DAFTAR SINGKATAN
Bcl-2
: B-cell lymphoma 2
Bfgf
: Basic fibroblast growth factor
CGH
: Comparative genomic hybridization
CO2
: Carbon dioxide
DAB
: Diaminobenzidine
DNA
: Deoxyribose nucleic acid
DPN
: Dermatosis papulosa nigra
FGFR3
: Fibroblast growth factor receptor 3
GM-CSF
: Granulocyte macrophage colony-stimulating factor receptor
HGF
: Hepatocyte growth factor
HPV-DNA
: Human Papilloma Virus- Deoxyribose nucleic acid
IL-1
: Interleukin-1
MC1R
: The melanocortin 1 receptor
PBS
: Phosphate buffered saline
PCR
: Polymerase chain reaction
PIK3CA
: Phosphatidylinositol-4,5-bisphosphate 3-kinase
RSUP
: Rumah Sakit Umum Pusat
RT-PCR
: Real time- polymerase chain reaction
SCF
: Stem cell factor
SMF
: Staf medik fungsional
TNF-α
: Tumour necrosing factor-α
Trekavidin-HRP
: Trekavidin-Horseradish Peroxidase
TRP-1
: Tyronase-related protein 1
UV
: Ultraviolet
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DAFTAR TABEL
No.
Judul
Halaman
Tabel 3.1 Tabel tingkatan ekspresi endotelin-1 .......................................................... 32
Tabel 4.1 Tabel distribusi objek penelitian berdasarkan variasi histopatologis ..........36
Tabel 4.2 Tabel distribusi ekspresi endotelin-1 berdasarkan variasi histopatologis ....37
Tabel 4.3 Tabel distribusi tingkatan ekspresi endotelin-1 berdasarkan variasi
histopatologis ..................................................................................................................38
Tabel 4.4 Tabel distribusi objek penelitian berdasarkan letak endotelin-1 .................42
Tabel 4.5 Tabel distribusi kekuatan ekspresi endotelin-1 berdasarkan letak endotelin-1
pada berbagai variasi histopatologis keratosis seboroik .................................................44
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DAFTAR GAMBAR
No.
Judul
Halaman
Gambar 2.1. Keratosis seboroik ................................................................................... 11
Gambar 2.2. Gambar histopatologis keratosis seboroik akantotik (umum)................... 13
Gambar 2.3. Gambar histopatologis keratosis seboroik reticulated ............................. 14
Gambar 2.4. Gambar histopatologis keratosis seboroik pigmented ............................... 14
Gambar 2.5. Gambar histopatologis keratosis seboroik klonal ..................................... 15
Gambar 2.6. Gambar histopatologis keratosis seboroik irritated .................................. 15
Gambar 2.7. Gambar histopatologis keratosis seboroik hiperkeratotik ........................ 16
Gambar 2.8. Gambar histopatologis keratosis seboroik flat ..........................................17
Gambar 2.9. Gambar histopatologis dermatosis papulose nigra ....................................18
Gambar 2.10.Gambar model sitokin parakrin hiperpigmentasi epidermal ...................23
Kerangka teori.................................................................................................................26
Kerangka konsep .............................................................................................................27
Kerangka operasional......................................................................................................35
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DAFTAR LAMPIRAN
No.
Judul
Halaman
Lampiran 1. Status penelitian......................................................................................... 55
Lampiran 2. Ethical Clearance ...................................................................................... 56
Lampiran 3. Data dasar penelitian ................................................................................. 57
Lampiran 3. Data gambar imunohistokimia................................................................... 59
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HISTOPATOLOGIS KERATOSIS SEBOROIK
TESIS
Oleh
dr. EVITA LOURDES PINEM
PROGRAM PENDIDIKAN DOKTER SPESIALIS
DEPARTEMEN ILMU KESEHATAN KULIT DAN KELAMIN
FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA
MEDAN
2017
Universitas Sumatera Utara
Ekspresi Endotelin-1 pada Berbagai Variasi Histopatologis Keratosis Seboroik
Evita Lourdes Pinem, Imam Budi Putra, Nelva Karmila Jusuf
Departemen Ilmu Kesehatan Kulit dan Kelamin
Fakultas Kedokteran Universitas Sumatera Utara
RSUP H. Adam Malik Medan
Abstrak:
Latar belakang: Keratosis seboroik adalah suatu tumor benigna yang terdiri dari keratinosit
epidermis dengan pigmentasi meningkat. Variasi histopatologis keratosis seboroik adalah:
akantotik, flat, irritated, stuccokeratosis, pigmented, reticulated, pedunculated, dermatosis
papulose nigra, dan klonal. Diduga bahwa melanisasi yang meningkat yang terobservasi pada
keratosis seboroik dikaitkan dengan produksi endotelin-1 yang meningkat pada proliferasi
keratinosit yang tinggi sehingga menimbulkan neoplasma.
Tujuan: Mengetahui ekspresi endotelin-1 pada berbagai variasi histopatologis keratosis
seboroik.
Metode: Penelitian ini menggunakan studi deskriptif observasional laboratoris dengan
rancangan potong lintang yang menggunakan 40 blok parafin yang telah diperiksa secara
histopatologis sebagai keratosis seboroik dan telah ditentukan variasi histopatologinya.
Hasil: Ekspresi endotelin-1 pada 14 sampel keratosis seboroik varian akantotik didapati kuat
4 sampel (28,57%), sedang 4 sampel (28,57%), dan lemah 6 sampel (42,85%), dan letak
endotelin-1 pada stratum basalis 9 sampel (64,28%), 1/3 bawah lapisan epidermis 1 sampel
(7,14%), dan seluruh lapisan epidermis 4 sampel (28,57%). Ekspresi endotelin-1 pada 6
sampel keratosis seboroik varian flat didapati kuat 1 sampel (16,67 %), sedang 2 sampel
(33,33%), dan lemah 3 sampel (50 %) dan letak endotelin-1 pada stratum basalis 5 sampel
(83,33%), dan 1/3 bawah lapisan epidermis 1 sampel (16,66%). Ekspresi endotelin-1 pada1
sampel keratosis seboroik varian irritated didapati lemah 1 sampel (100%) dan letak
endotelin-1 pada seluruh lapisan epidermis 1 sampel (100%). Ekspresi endotelin-1 pada 6
sampel keratosis seboroik varian stuccokeratosis didapati kuat pada 2 sampel (33,33 %),
sedang 1 sampel (16,67%), dan lemah 3 sampel (50%) dan letak endotelin-1 pada stratum
basalis 4 sampel (66,67%), 1/3 bawah lapisan epidermis 1 sampel (16,66%), dan seluruh
lapisan epidermis 1 sampel (16,66%). Ekspresi endotelin-1 pada 2 sampel keratosis seboroik
varian pigmented didapati kuat pada 2 sampel (100 %) dan letak endotelin-1 pada stratum
basalis 1 sampel (50%), dan seluruh lapisan epidermis 1 sampel (50%). Ekspresi endotelin-1
pada 7 sampel keratosis seboroik varian reticulated didapati kuat 1 sampel (14,28%), sedang
4 sampel (57,14%), dan lemah 2 sampel (28,57%) dan letak endotelin-1 pada stratum basalis
7 sampel (100%). Ekspresi endotelin-1 pada 1 sampel keratosis seboroik varian pedunculated
didapati sedang 1 sampel (100%) dan letak endotelin-1 pada lapisan stratum basalis 1 sampel
(100%). Ekspresi endotelin-1 pada 3 sampel keratosis seboroik varian dermatosis papulose
nigra didapati sedang 2 sampel (66,67%), dan lemah 1 sampel (33,33%) dan letak
endotelin-1 pada stratum basalis 2 sampel (66,67%), dan seluruh lapisan epidermis 1 sampel
(33,33%).
Kesimpulan: Dilihat dari ekspresi endotelin-1 pada berbagai variasi histopatologis keratosis
seboroik maka didapatkan ekspresi endotelin-1 yang kuat 25% (tipe akantotik 10%,
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stuccokeratosis 5%, pigmented 5%, flat 2,5%, dan reticulated 2,5%), sedang 35% (akantotik
10%, flat 5%, stuccokeratosis 2,5%, reticulated 10%, pedunculated 2,5%, dermatosis
papulose nigra 5%), dan lemah 40% (akantotik 15%, flat 7,5%, irritated 2,5%,
stuccokeratosis 7,5%, reticulated/ adenoid 5%, dan 1 dermatosis papulose nigra 2,5%).
Kata kunci: Keratosis seboroik, ekspresi endotelin-1.
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Endothelin-1 Expressions on Seborrheic Keratosis Histopathology Variants
Evita Lourdes Pinem, Imam Budi Putra, Nelva Karmila Jusuf
Dermatovenereology Department
University of Sumatera Utara Medical Faculty
H. Adam Malik Centre General Hospital Medan
Abstract
Background: Seborrheic keratosis is a benign tumor, composed of keratynocites with
increased pigmentation. Seborrheic keratosis histopathological variants are acanthotic, flat,
irritated, stuccokeratosis, pigmented, reticulated, pedunculated, dermatosis papulose nigra,
and klonal. It suggested that the enhanced pigmentation in seborrheic keratosis is attributable
to the upregulated expression of endothelin-1 by highly proliferating basaloid cells.
Objective: To describe endothelin-1 expression on seborrheic keratosis histopathological
variants.
Materials and Methods: This study was descriptive observasional and cross sectional study,
used 40 samples of seborrheic keratosis’ lesions that diagnosed based on histopathological
examinations, and the histopathological variants have determined.
Result: Endothelin-1 expressions of 14 acanthotic variants were strong 4 samples (28,57%),
moderate 4 samples (28,57%), and weak 6 samples (42,85%) and endothelin-1 was located
in stratum basale 9 samples (64,28%), one-third lower part of the epidermis 1 sample
(7,14%), and epidermis 4 samples (28,57%). Endothelin-1 expressions of 6 flat variants were
strong 1 sample (16,67%), moderate 2 samples (33,33%), and weak 3 samples (50%) and
endothelin-1 was located in stratum basale 5 samples (83,33%) and one-third lower part of
the epidermis 1 sample (16,66%). Endothelin-1 expression of 1 irritated variant was weak 1
sample (100%) and endothelin-1 was located in epidermis 1 sample (100 %). Endothelin-1
expressions of 3 stuccokeratosis variants were strong 2 samples (33,33%), moderate 1
sample (16,67%), and weak 3 samples (50%) and endothelin-1 was located in stratum basale
4 samples (66,67%), one-third lower part of the epidermis 1 sample (16,66%), and epidermis
1 sample (16,66%). Endothelin-1 expressions of 2 pigmented variants were strong 2 (10%)
and endothelin-1 was located in stratum basale 1 sample (50%), and epidermis 1 sampel
(50%). Endothelin-1 expressions of 7 reticulated variants were strong 1 sampel (14,28%),
moderate 4 samples (57,14%), and weak 2 samples (28,57%) and endothelin-1 was located in
stratum basale 7 samples(100%). Endothelin-1 expression of 1 pedunculated variant was
moderate 1 sample (100%) and endothelin-1 was located in stratum basale 1 sample (100%).
Endothelin-1 expressions of 3 dermatosis papulose nigra variants were moderate 2 samples
(66,67%) and weak 1 sample (33,33%) and endothelin-1 was located in stratum basale 2
samples (66,67%) and epidermis 1 sample (33,33%).
Conclusion: Endothelin-1 expressions of seborrheic keratosis histopathological variants were
strong 25% (acanthotic 10 %, stuccokeratosis 5%, pigmented 5%, flat 2,5%, and reticulated
2,5%), moderate 35% (acanthotic 10%, flat 5%, stuccokeratosis 2,5%, reticulated 10%,
pedunculated 2,5%, dermatosis papulose nigra 5%), and weak 40% (acanthotic 15%, flat
7,5%, irritated 2,5%, stuccokeratosis 7,5%, reticulated/adenoid 5% and dermatosis papulose
nigra 2,5%).
Key words: seborrheic keratosis, endothelin-1 expression.
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DAFTAR ISI
Halaman
ABSTRAK ................................................................................................................ i
ABSTRACT ........................................................................................................... iii
DAFTAR ISI ........................................................................................................... iv
DAFTAR SINGKATAN ....................................................................................... vi
DAFTAR TABEL..................................................................................................vii
DAFTAR GAMBAR ........................................................................................... viii
DAFTAR LAMPIRAN ........................................................................................... ix
BAB I
PENDAHULUAN ................................................................................ 1
1.1 Latar Belakang ............................................................................ 1
1.2 Rumusan Masalah........................................................................ 3
1.3 Tujuan Penelitian ......................................................................... 3
1.3.1 Tujuan umum...................................................................... 3
1.3.2 Tujuan khusus ..................................................................... 3
1.4 Manfaat penelitian ....................................................................... 5
1.4.1. Akademik........................................................................... 5
1.4.2. Penelitian ........................................................................... 5
BAB II
TINJAUAN PUSTAKA ....................................................................... 6
2.1 Keratosis Seboroik ....................................................................... 6
2.1.1. Epidemiologi .................................................................... 6
2.1.2. Etiopatogenesis ................................................................ 7
2.1.3. Faktor risiko ..................................................................... 9
2.1.4. Gambaran klinis.............................................................. 10
2.1.5. Diagnosis banding ......................................................... 11
2.1.6. Diagnosis ........................................................................ 12
2.1.7 Variasi histopatologis ..................................................... 12
2.1.8. Penatalaksanaan .............................................................. 18
2.1.9. Prognosis ........................................................................ 21
2.2 Endotelin-1 ................................................................................ 21
2.3 Fungsi Endotelin-1 .................................................................... 21
2.4 Peran Endotelin-1 pada Keratosis Seboroik.............................. 22
2.5 Kerangka Teori ......................................................................... 26
2.6 Kerangka Konsep ..................................................................... 27
BAB III
METODE PENELITIAN .................................................................... 28
3.1 Desain Penelitian ....................................................................... 28
3.2 Waktu dan Tempat Penelitian.................................................... 28
3.3 Sampel Penelitian ...................................................................... 28
3.4 Besar Sampel ............................................................................. 29
3.5 Cara Pengambilan Sampel penelitian ........................................ 30
3.6 Definisi Operasional .................................................................. 30
3.7 Alat, Bahan dan Cara Kerja ....................................................... 32
3.7.1 Alat… ........................................ …………………………32
3.7.2 Bahan… ................................. ……………………………32
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3.7.3 Cara kerja… .......................... ……………………………33
3. 8 Kerangka Operasional ................................................................ 35
3. 9 Ethical Clearance ...................................................................... 35
BAB IV
HASIL PENELITIAN DAN PEMBAHASAN .................................. 36
4.1 Variasi Histopatologis ............................................................... 36
4.2 Hasil Pemeriksaan Imunohistokimia ........................................ 37
4.2.1 Ekspresi endotelin-1 berdasarkan
variasi histopatologis- nya ............................................... 37
4.2.2 Letak endotelin-1 ............................................................. 42
4.2.3 Ekspresi dan letak endotelin-1 berdasarkan variasi ..............
histopatologisnya .............................................................. 44
BAB V
KESIMPULAN DAN SARAN ........................................................... 47
5.1 Kesimpulan ................................................................................ 47
5.1 Saran .......................................................................................... 48
DAFTAR PUSTAKA ............................................................................................ 49
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DAFTAR SINGKATAN
Bcl-2
: B-cell lymphoma 2
Bfgf
: Basic fibroblast growth factor
CGH
: Comparative genomic hybridization
CO2
: Carbon dioxide
DAB
: Diaminobenzidine
DNA
: Deoxyribose nucleic acid
DPN
: Dermatosis papulosa nigra
FGFR3
: Fibroblast growth factor receptor 3
GM-CSF
: Granulocyte macrophage colony-stimulating factor receptor
HGF
: Hepatocyte growth factor
HPV-DNA
: Human Papilloma Virus- Deoxyribose nucleic acid
IL-1
: Interleukin-1
MC1R
: The melanocortin 1 receptor
PBS
: Phosphate buffered saline
PCR
: Polymerase chain reaction
PIK3CA
: Phosphatidylinositol-4,5-bisphosphate 3-kinase
RSUP
: Rumah Sakit Umum Pusat
RT-PCR
: Real time- polymerase chain reaction
SCF
: Stem cell factor
SMF
: Staf medik fungsional
TNF-α
: Tumour necrosing factor-α
Trekavidin-HRP
: Trekavidin-Horseradish Peroxidase
TRP-1
: Tyronase-related protein 1
UV
: Ultraviolet
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DAFTAR TABEL
No.
Judul
Halaman
Tabel 3.1 Tabel tingkatan ekspresi endotelin-1 .......................................................... 32
Tabel 4.1 Tabel distribusi objek penelitian berdasarkan variasi histopatologis ..........36
Tabel 4.2 Tabel distribusi ekspresi endotelin-1 berdasarkan variasi histopatologis ....37
Tabel 4.3 Tabel distribusi tingkatan ekspresi endotelin-1 berdasarkan variasi
histopatologis ..................................................................................................................38
Tabel 4.4 Tabel distribusi objek penelitian berdasarkan letak endotelin-1 .................42
Tabel 4.5 Tabel distribusi kekuatan ekspresi endotelin-1 berdasarkan letak endotelin-1
pada berbagai variasi histopatologis keratosis seboroik .................................................44
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DAFTAR GAMBAR
No.
Judul
Halaman
Gambar 2.1. Keratosis seboroik ................................................................................... 11
Gambar 2.2. Gambar histopatologis keratosis seboroik akantotik (umum)................... 13
Gambar 2.3. Gambar histopatologis keratosis seboroik reticulated ............................. 14
Gambar 2.4. Gambar histopatologis keratosis seboroik pigmented ............................... 14
Gambar 2.5. Gambar histopatologis keratosis seboroik klonal ..................................... 15
Gambar 2.6. Gambar histopatologis keratosis seboroik irritated .................................. 15
Gambar 2.7. Gambar histopatologis keratosis seboroik hiperkeratotik ........................ 16
Gambar 2.8. Gambar histopatologis keratosis seboroik flat ..........................................17
Gambar 2.9. Gambar histopatologis dermatosis papulose nigra ....................................18
Gambar 2.10.Gambar model sitokin parakrin hiperpigmentasi epidermal ...................23
Kerangka teori.................................................................................................................26
Kerangka konsep .............................................................................................................27
Kerangka operasional......................................................................................................35
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Universitas Sumatera Utara
DAFTAR LAMPIRAN
No.
Judul
Halaman
Lampiran 1. Status penelitian......................................................................................... 55
Lampiran 2. Ethical Clearance ...................................................................................... 56
Lampiran 3. Data dasar penelitian ................................................................................. 57
Lampiran 3. Data gambar imunohistokimia................................................................... 59
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