α_vβ₆Integrin-A Marker for the Malignant Potential of Epithelial Ovarian Cancer

Abstract

The mechanism(s) responsible for the progression of non-metastatic or borderline ovarian cancer to invasive Grade I/III ovarian cancer is still unknown. An epithelium-restricted integrin, αvβ6, is present in malignant epithelia but not in normal epithelia. We studied the relative expression and distribution of αvβ6 integrin in early and late-stage invasive (Grade I and Grade III) and non-invasive (benign and borderline) ovarian tumors of serous, mucinous, endometrioid, and clear-cell carcinoma subtypes, to assess its potential as a marker for epithelial ovarian cancer progression. Sixty-six specimens, including eight normal, 13 benign, 14 borderline, 13 Grade I, and 18 Grade III tumors were evaluated by immunohistochemistry (IHC) using a monoclonal antibody (MAb) against αvβ6 integrin. Normal ovarian surface epithelium was negative for αvβ6 integrin expression. All 45 carcinomas studied were positive, and the staining intensity significantly correlated with the grade of the tumor. The Grade III carcinomas of all types showed strong staining intensity. Only mucinous benign tissues were positive, and no reactivity was observed in benign serous neoplasms. On the basis of these observations, we hypothesize that the expression of αvβ6 integrin is associated with epithelial ovarian cancer and that a gradual increase in the expression of the molecule may be a correlative index of the progression of this disease.

Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial–mesenchymal transition in ovarian carcinomas

“…Immunohistochemical analysis on ovarian tissues was performed as described previously (Ahmed et al, 2002a(Ahmed et al, , b, 2003. Briefly, paraffin sections were cut at 4 mm thickness, mounted on silane-coated slides and incubated overnight at 371C.…”

High expression of integrin β6 in association with the Rho–Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers

“…There is now overwhelming evidence for its role in the clinical progression of multiple human epithelial malignancies (colon, ovary, and brain), both from the in situ to the invasive stage as well as from the invasive stage to regional and distant metastasis 5, 6, 7. The addition of breast cancers to this long list of epithelial cancers where integrin α v β 6 plays a role in clinical progression is more recent.…”

Conversion of a tumor-binding peptide identified by phage display to a functional chimeric T cell antigen receptor

“…These observations corroborate previous studies demonstrating that expression of integrin avb6 is associated with epithelial ovarian cancer. 7 We next evaluated the ability of Bpep-CAR þ CTL to specifically kill avb6 þ cancer cell targets. The bulk line and CTL clones A9 and A11 were co-cultured with OVCAR-3, RSN001 and RSN002 in a chromium release assay (CRA) at E:T ratios of 50:1, 25:1, 5:1 and 1:1 in triplicate.…”

“…6 Expression of avb6 has also been demonstrated in ovarian, pancreatic, colonic and oral squamous cell carcinomas. 6,7 The staining intensity of avb6 seems to correlate with the grade of ovarian cancer, and can distinguish benign from malignant neoplasms. 7 Moreover, avb6 integrin may be integrally linked to the malignant phenotype of tumors as this integrin promotes tumor invasion and metastasis by regulating collagenase production.…”

“…6,7 The staining intensity of avb6 seems to correlate with the grade of ovarian cancer, and can distinguish benign from malignant neoplasms. 7 Moreover, avb6 integrin may be integrally linked to the malignant phenotype of tumors as this integrin promotes tumor invasion and metastasis by regulating collagenase production. 8 Given that avb6 integrin is selectively expressed on carcinoma cells and linked to high-risk metastatic disease, it is an attractive target for immunotherapy.…”