Vaginal Squamous Cell Carcinoma and Intraepithelial Neoplasia Do Not Express Selected Junctional Markers Expressed in Cervical Carcinoma
Cynthia Jimenez, Christopher P Crum, Michael Herfs. Brigham and Women's Hospital, Boston, MA
Background: Vaginal squamous cell carcinoma (SCC) is rare, accounting for only 1 % to 2% of all gynecologic malignancies. Similar to cervical squamous cell carcinoma, vaginal SCC and its precursor (vaginal intraepithelial neoplasia), has a strong association with human papillomavirus (HPV) infection and lesions contain a wider range of HPV types. Although the estimates of persistent oncogenic HPV infections are similar in cervical and vaginal lesions the incidence rates of cervical cancers are much higher. Recently a discrete population of cervical squamocolumnar junction (SCJ) cells was identified that have a specific morphology and gene expression profile. These SCJ cells were found to be immunoreactive with junction-specific antibodies including keratin 7 (Krt7). The aim of this study was to determine if vaginal squamous cell carcinomas and their precursor lesions develop from SC junction cells.
Design: 28 vaginal biopsies, including 6 VAIN1 (LSIL), 14 VAIN 2/3 (HSIL) and 8 invasive squamous cell carcinomas were studied. All cases were evaluated for Krt7 and p16 expression by immunohistochemistry. Staining for p16 was classified as patchy or horizontally diffuse. History of cervical intraepithelial carcinoma and follow-up information were obtained from patients medical records.
Results: Immunohistochemical staining with Krt 7 was positive in 0/6 (0%) of VAIN1 cases, 2/14 (14%) of VAIN 2/3 cases and 1/8 (12%) of invasive squamous cell carcinomas. The incidence of concurrent or prior cervical squamous intraepithelial lesions was similar to previous reports. All cases of VAIN1 were negative for p16. One case of VAIN2/3 had patchy p16 staining; the remaining cases of VAIN2/3 had horizontally diffuse p16 staining.
Conclusions: This study confirms that most vaginal SILs and invasive squamous cell carcinomas do not arise from SCJ cells. This supports the more traditional mechanism of HPV lesion formation in this site, being disruption of the basal epithelium and infection of basal keratinocytes. It also explains the marked differences in lesion incidence between the cervix and vagina and underscores the fact that the vagina is not protected from SIL following removal of the cervix. Whether occasional SCJ positive SILs or carcinomas arise by extension of prior cervical lesions, or develop from residual embryonic SCJ cells is unknown.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 228, Tuesday Afternoon