Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 5036
© 2004 American Society of Clinical Oncology

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Abstract

Association of lymphatic vessel invasion and progression of cervical cancer with focused expression of CD9

University of Ulm Medical School, Ulm, Germany

5036

Background: Lymphovascular space invasion plays a critical role in the progression of cervical cancer. It is responsible for an unfavorable prognosis even in patients with early stage disease. The identification and functional characterization of molecules that are differently expressed in tumors with lymphatic vessel involvement in comparison to those without are of particular interest. For a number of malignant diseases, the level of CD9 expression a transmembrane protein involved in various fundamental cellular processes was found to be inversely correlated with tumor invasiveness, ability to form metastases, and poor clinical outcome. We demonstrate that carcinomas of the cervix locally re-express CD9 at sites of lymphatic space invasion. This suggests its functional involvement in transendothelial migration as a crucial step in the formation of lymph node metastases. Methods: Formalin-fixed, paraffin-embedded surgical specimens of 44 consecutive patients with invasive cervical cancer were examined. These consisted of 11 patients without lymph node metastases, 15 patients with metastases to pelvic lymph nodes, and 18 patients with lymphangiogenesis and lymph node metastases. To determine the role of CD9 in lymphovascular space invasion, immunohistochemical doublestaining was performed with monoclonal mouse antibodies binding to CD9 and CD34. Results: CD9 was frequently found to be downregulated in the main tumor mass whereas it was still highly expressed at sites of tumor cell invasion (CD9 hotspots). The appearance of CD9 hotspots turned out to be a high significant (p < 10–5) indicator of lymphatic vessel and invasion disease recurrence. Conclusions: Our observation that CD9 is predominately expressed by clusters of cervical carcinoma cells close to vessels and in the process of transendothelial transition evidently supports a key function of tumor cell CD9 at heterologous cell-cell contacts. This parameter may be used as an indicator of poor prognosis in cases with unclear or unknown histopathological assessment and may define a subgroup of patients that may benefit from additional treatment.

No significant financial relationships to disclose.

Abstract presentation from the 2004 ASCO Annual Meeting