Expression of Endogenous Hypoxia Markers in Vulvar Squamous Cell Carcinoma

Abstract

Objective: To investigate the expression of endogenous hypoxia-related markers identified as being involved in vulvar squamous cell carcinoma (VSCC). Methods: We performed immunohistochemical staining of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), carbonic anhydrase 9 (CA-9) and vascular endothelial growth factor (VEGF), on tissue sections of 25 VSCC patients, 10 vulvar intraepithelial neoplasia (VIN) patients and 12 healthy controls. Results: HIF-1α expression was found in all sections, with no significant difference between controls, VIN and VSCC sections (all P<0.05). Glut-1 expression was found in 25% of control, 90% of VIN and 100% of VSCC sections. A significant difference between control and VIN or VSCC was observed (all P<0.05), while no difference was found between VIN and VSCC sections (P>0.05). CA-9 expression was negative in control sections, but it was found in 30% of VIN sections and 52% of VSCC sections with strong staining. Similarly, CA-9 expression also showed obvious differences between controls and VIN or VSCC sections (all P<0.05). However, there was no significant difference between VIN and VSCC (P>0.05). There were only 25% of control sections with weak VEGF expression, while strong staining was found in about 60% of VIN sections and 25% of VSCC sections (all P<0.05). In addition, a difference was also found between VIN and VSCC sections (P<0.05). Conclusion: Expression of endogenous hypoxia markers (HIF-1α, GLUT-1, CA-9 and VEGF) might be involved in the malignant progression of VSCC.

Primary Tumor Vascularity, HIF-1α and VEGF expression in vulvar squamous cell carcinomas: their relationships with clinicopathological characteristics and prognostic impact

“…An increasing expression of VEGF from normal epithelium to premalignant lesion to invasive squamous cell carcinoma was found in vulva [28]. In the present study, high VEGF expression was significantly associated with only poor tumor differentiation, however, an other study reported no such association in vulvar carcinomas [19].…”

“…Hypoxia markers; HIF-1α, GLUT-1, CA IX and VEGF are expressed in both vulvar preneoplastic lesions and invasive squamous cell carcinoma [28]. An increasing expression of VEGF from normal epithelium to premalignant lesion to invasive squamous cell carcinoma was found in vulva [28].…”

“…The relation between primary tumor vascularity and HIF-1α expression in head and neck and oesophageal squamous cell carcinoma has been reported [24,25], and the prognostic impact of HIF-1α expression in cancer is varied [26,27,29-32]. HIF-1α expression investigated recently in normal epithelium, intraepithelial neoplasia and invasive carcinoma of vulva did not show significant differences [28]. To our knowledge, no study of HIF-1α expression and its connection with prognosis in vulvar carcinoma patients has been reported.…”

“…VEGF, a potent angiogenic molecule over-expressed in a hypoxic state, is crucial to induce tumor angiogenesis and acts through the receptors VEGFR1 and VEGFR2 [22,33]. It is expressed in various human cancers including vulvar malignancy [21,28,34,35]. A significant variation in expression of VEGF in nonneoplastic epithelium, preneoplastic lesions and invasive squamous cell carcinoma of vulva has been described [21,28,35].…”

“…It is expressed in various human cancers including vulvar malignancy [21,28,34,35]. A significant variation in expression of VEGF in nonneoplastic epithelium, preneoplastic lesions and invasive squamous cell carcinoma of vulva has been described [21,28,35]. Its expression in vulvar cancer and relationship with vascularity has been reported [19].…”