Rare Cervical Cancers: Immunohistochemistry and Correlation with HPV Infection Status by In-Situ Hybridization and Linear Array.
Ghassan Allo, Ming Tsao, Marjan Rouzbahman, Cuihong Wei, Suzanne Kamel-Reid, Golnar Rasty. University Health Network, Toronto, ON, Canada
Background: Human papilloma virus (HPV) is a major etiologic factor in the development of cervical epithelial malignancies. Limited data is available on the less common cervical tumors. Our aim is to examine HPV status, and its correlation with immunohistochemical expression in rare cervical carcinomas and mixed tumors.
Design: Pathology archives at the department of Anatomic Pathology, were searched for primary cervical carcinomas excluding squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma from 2000 till now. 34 cases were retrieved which include adenoid basal (AB) carcinoma (n=2), clear cell (CC) carcinoma (n=2), glassy cell (GL) carcinoma (n=2), lymphoepithelioma – like (LE) carcinoma (n=3), serous (SR) carcinoma (n=9), villoglandular (VG) carcinoma (n=4), and neuroendocrine (NE) carcinoma (small cell, large cell, mixed carcinomas). The histopathology was reviewed by 2 pathologists. Chromogenic in-situ hybridization (CISH) –INFORM HPV (13 genotypes) and Roche Linear array HPV genotyping (37 genotypes) were performed on all cases. The following immunoperoxidase stains were performed on tissue microarray: (LMWK),CK 5/6,p16, p63, p53, Synaptophysin, Chromogranin, CD56, ER, PR, TTF-1, WT-1 and Ki67.
Results: High risk HPV-DNA is identified in 30% of serous carcinoma and 75% of NE carcinoma. Expression of NE markers in mixed NE carcinoma suggest pluripotential nature of the tumor. p16 is expressed in almost all tumors. p53 is mainly expressed in CC and GL with no expression in serous carcinoma of cervix. WT-1 is negative in all cervical carcinomas.
|Cases||p16||p63||p53||NE marker||HPV status||HPV+/case #|
|AB||1+, 30-60%||3+, 100%||<10%||0||-/+||1/2|
|CC||3+, 100%||0||2+, 30-60%||0||-||0/2|
|GL||2+, 50%||2+, 100%||2+, 30-60%||0||+||1/2|
|LE||2+, 100%||3+, 100%||0||0||+||2/3|
|NE||2+, 100%||3+, 10%||<5%||75%||+||9/12|