Objective: Although CXC chemokine receptor type 4 (CXCR4) is known to be expressed in various solid tumors and plays an integral role in cancer invasion and metastasis, expression of CXCR4 in human vulvar cancer has not yet been investigated. We examined distribution and expression of this chemokine receptor in specimens of invasive and noninvasive human vulvar neoplasms to elucidate its clinical significance.
Methods: Study patients were 38 consecutive patients (31 with primary vulvar cancers and 7 with intraepithelial neoplasms) treated at one of our hospitals. Sections of all specimens were evaluated for CXCR4 expression by means of immunohistochemistry. Relations between CXCR4 expression and clinicopathologic features including prognosis were investigated.
Results: None of the 7 vulvar intraepithelial lesions expressed CXCR4. Of the 31 invasive vulvar tumor samples examined, 19 (61%) stained positively for CXCR4; 15 (68%) of 22 squamous cell carcinomas and 2 (29%) of 7 Paget tumors were CXCR4 positive. The difference in expression between invasive cancers and intraepithelial neoplasms was significant (P = 0.003). FIGO (International Federation of Gynecology and Obstetrics) stage III-IV cancers, in comparison to FIGO stage I-II cancers, were more likely to be positive for CXCR4 (82% vs 50%, P = 0.08). In terms of disease-free survival, prognosis of cancers that expressed CXCR4 was poorer than that of CXCR4-negative cancers (P = 0.013), but in terms of disease-specific survival, prognosis did not differ significantly between CXCR4-positive and -negative cancers (P = 0.111).
Conclusions: More than half of invasive squamous cell vulvar cancers can be expected to express CXCR4, and CXCR4 expression correlates with poor disease prognosis.