EXPRESSION OF p53 AND p63 IN CERVICAL SQUAMOUS CELL CARCINOMA; THEIR ASSOCIATION WITH CANCER CELLS PROLIFERATION, MORPHOLOGY, AND FIGO STAGING

ILHAMI ROMUS, dr. harjadi, Sp.PA(K)

2013 | Tesis | S2 Ilmu Patologi Anatomi

Latar Belakang: Hubungan infeksi Human Papilloma Virus (HPV) dengan potensi karsinogenesis pada kanker servik telah lama diketahui. E6 dan E7 mengikat produk p53 dan gen retinoblastoma, sehingga fungsi p53 dan pRB sebagai penekan tumor serta pengaturan siklus sel terganggu. Namun, dari hasil penelitian-penelitian tentang ekspresi p53 pada kanker serviks masih banyak yang bertentangan. Penelitian terbaru pada tahun 2011 menjelaskan pada sel karsinoma serviks, E6 menyebabkan degradasi TAp63b yang memungkinkan terjadinya pertumbuhan sel. p53 dan homolognya p63 memiliki peran dalam patogenesis kanker servik khususnya karsinoma sel skuamousa. Tujuan: Penelitian ini akan menganalisa ekspresi p53 dan p63 pada karsinoma sel skuamosa leher rahim dan dihubungkan dengan indeks proliferasi sel (Ki-67), morfologi, dan FIGO staging. Metode: Penelitian ini dilakukan secara cross sectional dengan pengecatan imunohistokimia menggunakan antibodi monoklonal anti p63, p53, Ki-67 terhadap 56 blok parafin jaringan karsinoma sel skuamousa leher rahim dalam periode tahun 2010-2011 di RS Dr.Sardjito. Masing – masing ekspresi gen ini akan dihubungkan dengan indeks proliferasi sel, morfologi dan staging. Hubungan antara ekspresi p53 dan p63 terhadap morfologi dan FIGO staging dianalisa dengan uji Mann-Whitney. Sedangkan korelasi antara ekspresi p53 dan p63 terhadap Ki-67 dianalisa dengan uji Spearman. Statistik dianggap signifikan jika nilai p<0,05. Hasil: Usia rata-rata pasien saat terdiagnosis adalah 54,23 tahun. Rerata ekspresi p53 pada penelitian ini adalah 43,23% (range 0%-87%0, sedangkan p63 78,64% (range 3%-98%). Perbedaan rerata ini sangat signifikan (p=0,00). Pada penelitian ini didapatkan hubungan yang signifikan antara ekspresi p53 dengan usia (p = 0,019) dan FIGO staging (p=0,026), tidak ada hubungan yang signifikan terhadap morfologi dan Ki-67. Sedangkan pada ekspresi p63 tidak didapatkan hubungan yang signifikan terhadap usia, morfologi, FIGO staging dan KI-67. Pada penelitian ini, didapatkan 1 sampel dengan ekspresi p63 negatif (<15%) yang selanjutnya dinilai sebagai adenokarsinoma differensiasi buruk. Kesimpulan: Penelitian ini mengasumsikan bahwa p53 memiliki nilai prognostik dalam kaitannya dengan FIGO staging, sedangkan p63 lebih bernilai diagnostik karena perannya dalam differensiasi sel skuamosa pada leher rahim yang terekspresi positif kuat pada hampir semua sampel pada penelitian ini.

Background: Human papilloma virus infection has been associated with carcinogenesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Recent study in 2011 identified the role of p53 homolog p63 in cervical carcinoma cells, which describes E6 expression therefore leads to TAp63b degradation thereby allowing anchorage independent growth. According to their role in cervical cancer, both of p53 and p63, molecular studies correlated with several clinicopathological factors are important to determine diagnosis, prognosis and treatment strategies, but they showed controversial results and need to be clarified. Aim: To investigate expression of p53 and p63 in cervical squamous cell carcinoma and correlate with age, FIGO staging, morphology, and cancer cells proliferation. Methods: Using cross sectional study, the expression of p53 and p63 immunohistochemical staining of totally 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, were evaluated. The correlation of those markers expression with clinicopathological parameters as patients age, FIGO staging, morphology, and cancer cells proliferation were investigated. Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean of p53 and p63 expression. While, Spearman correlation test was used to correlate percentage of p53 and p63 expression with percentage of Ki-67 expression. A p-value of <0.05 was considered statistically significant. Result: The results of p53 expression in our study are in the range of 0%-87% with mean 43,23%. While, p63 expression were in the range of 3%-98% with mean 78,64%. The difference mean of p53 and p63 expression were analyzed with Mann Whitney test with very significant result (p < 0,00).There were significant association between p53 expression with age (p=0,019) and FIGO staging (p=0,026), and no significant association with morphology and Ki-67 expression. There were no significant association between p63 expression with age, morphology, FIGO staging and Ki-67. Summary: This study assumed that p53 has a prognostic value in cervical squamous cell carcinoma that the expression of this gene has associated with FIGO staging. While p63 has a diagnostic value in cervical squamous cell carcinoma because its role in squamous cell differentiation.

Kata Kunci : P63, p53, Ki67, morfologi, FIGO staging, karsinoma sel skuamosa leher rahim