Prognostic Significance of Cell Cycle- and Invasion-Related Molecular Markers and Genomic Instability in Primary Carcinoma of the Vagina

Hellman, Kristina MD, PhD*; Johansson, Hemming BS; Andersson, Sonia MD, PhD; Pettersson, Folke MD, PhD*; Auer, Gert MD, PhD§

International Journal of Gynecological Cancer: January 2013 - Volume 23 - Issue 1 - p 41–51
doi: 10.1097/IGC.0b013e31827670c4
Basic Science

Objective: This study aimed to analyze the prognostic value of DNA content and biological markers for cell cycle regulation and invasion in primary carcinoma of the vagina (PCV).

Material and Methods: Seventy-two consecutive patients with PCV, categorized as short-term (≤2 years) and long-term (≥8 years) survivors, were evaluated for DNA content by image cytometry, and for expression of p53, p21, cyclin A, Ki67, E-cadherin, and laminin-5γ2 chain by immunohistochemistry. The relationship between these biological markers and histopathological and clinical parameters was assessed.

Results: All PCV showed aneuploid DNA content. Most of the PCV patients showed no overexpression of p53 and high expression of p21, cyclin A, and Ki67. Loss or underexpression of E-cadherin was found in 94% (68/72) of PCV patients, and all patients showed immunopositivity for the laminin-5γ2 chain. Tumors with a vaginal longitudinal location in the lower third or in the entire vagina more often had overexpression of p53, high expression of Ki67 (P = 0.044), and underexpression of E-cadherin (P = 0.038), than tumors confined only to the upper third. Overexpression of p53 was significantly associated with short-term survival in the univariate analysis, but not in the multivariate analysis adjusted for age at diagnosis and tumor size.

Conclusions: The expression level of some markers was related to tumor location, which might be indicative of different genesis. Overexpression of p53 was associated with short-term survival, but the only independent predictors of survival were age at diagnosis and tumor size.

Departments of *Gynecological Oncology, †Biostatistics and Oncology, Radiumhemmet, ‡Women’s and Children’s Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Elevhemmet H2:00, and §Oncology-Pathology, Karolinska Biomics Center, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Address correspondence and reprint requests to Kristina Hellman, MD, PhD, Department of Gynecological Oncology, Radiumhemmet, Karolinska University Hospital, 17176 Stockholm, Sweden. E-mail: kristina.hellman@ki.se.

Supported by the Swedish Cancer Foundation, Swedish Research Council, Medical Research Council, and Cancer Society in Stockholm, Stockholm County Council.

The authors declare no conflicts of interest.

Received June 15, 2012

Accepted September 27, 2012

Copyright © 2013 by IGCS and ESGO