Original Article

Modern Pathology (2006) 19, 708–716. doi:10.1038/modpathol.3800580; published online 10 March 2006

Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation

Presented in part at the 94th Annual Meeting of the United States and Canadian Academy of Pathology, February 26–March 4, 2005, San Antonio, TX, USA.

Kimberly L Dumoff1, Christina S Chu2, Eleanor E Harris3, David Holtz4, Xiaowei Xu1, Paul J Zhang1 and Geza Acs1

  1. 1Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA
  2. 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia, PA, USA
  3. 3Department of Radiation Oncolology, University of Pennsylvania Medical Center, Philadelphia, PA, USA
  4. 4Department of Obstetrics and Gynecology, Lankenau Hospital, Wynnewood, PA, USA

Correspondence: Dr G Acs, MD, PhD, Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Room 2071M, 12902 Magnolia Drive, Tampa, FL 33612, USA. E-mail: acsg@moffitt.usf.edu

Received 27 December 2005; Revised 7 February 2006; Accepted 7 February 2006; Published online 10 March 2006.

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Abstract

Lymphatic invasion and nodal metastasis are predictors of poor outcome in cervix carcinoma. We have recently found that low podoplanin immunoreactivity in cervix carcinoma correlated with the presence of lymphatic invasion and nodal metastasis. In the current study, we examined whether podoplanin expression in pretreatment cervical biopsies can predict the presence lymphatic invasion, nodal metastasis, and outcome in advanced-stage tumors treated by nonsurgical means. Podoplanin expression was analyzed by immunohistochemistry in 48 cervical biopsies and corresponding hysterectomy specimens of early-stage invasive squamous cell carcinoma and in 74 pretreatment biopsies from advanced-stage tumors treated with primary radiation. We found a highly significant correlation between podoplanin expression obtained in biopsy and corresponding hysterectomy materials (r=0.8962, P<0.0001). Low podoplanin expression showed a significant correlation with lymphatic invasion (P<0.0001) and nodal metastasis (P=0.0058). Low podoplanin expression in pretreatment biopsy material showed a significant correlation with poor disease-free (P=0.0009) and overall (P=0.0002) survival in advanced-stage tumors. Our results suggest that in advanced-stage cervix carcinomas treated by radiation, when traditional prognostic indicators are not available and treatment decisions are based on biopsy material and clinical staging parameters, examination of podoplanin expression in pretreatment biopsy material may be a useful marker to predict lymphatic metastasis and patient outcome. Prospective studies involving larger numbers of patients are needed to further evaluate the clinical utility of examination of podoplanin expression in patients with cervix carcinoma.

Keywords:

podoplanin, D2-40 antibody, cervix carcinoma, lymphatic invasion, lymph node metastasis, prognostic marker

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