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Relationship of HIF-1α, PCNA and VEGF with Microvascular Density in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma

Author: LiuYiQing
Tutor: ZhangJianWen
School: Zhengzhou University
Course: Surgery
Keywords: Skin tumors Hypoxia-inducible factor -1α Proliferating cell nuclear antigen CD105 Microvessel density
CLC: R739.5
Type: Master's thesis
Year: 2007
Downloads: 137
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Abstract

Background and Purpose cutaneous squamous cell carcinoma (squamous cell carcinoma, SCC) and basal cell carcinoma (basal cell carcinoma, BCC) is a common skin malignancy in orthopedic generally malignant uncontrolled sustained proliferation, invasion and metastasis characteristics . Hypoxia is one of the basic characteristics of the solid tumor microenvironment, tumor proliferation, angiogenesis and its material and energy metabolism adaptation is the basis of its survival and invasion. Studies have shown that for many malignant tumors, hypoxia-inducible factor-1α (hypoxia inducible factor-1α, HIF-1α) plays a central link and adjust and adapt to their own sexual. HIF-1α is a specific adaptive responses mediated by hypoxia transcription factor, vascular endothelial growth factor (vascular endothelial growth factor, VEGF) found the most pro-angiogenic factor, both through a variety of The pathway is involved in the process of malignant tumor. CD105 (endoglin) neovascular endothelial cell-specific marker of microvascular density (microvascular density, MVD) is recognized as the most effective objective indicators reflect tumor angiogenesis. Proliferating cell nuclear antigen (proliferating cell nuclear antigen, PCNA) is a nuclear protein, proliferating cell nuclear antigen amount to a significant change in the cell proliferation cycle, to better reflect the proliferative status. Currently, anti-cancer therapy targeting HIF-1α study the new hot spot, but the relationship between HIF-1α and tumor cell proliferation inconclusive, HIF-1α and VEGF in skin SCC, BCC and cell proliferation, vascular generate joint detection of very little, not yet reported. In this study, the method of immunohistochemical detection of skin SCC and BCC in HIF-1α, VEGF expression, PCNA-labeled cells in a proliferative state and calculate the proliferation index (proliferation index, PI), and calculate the value of MVD marked by CD105 neovascularization explore with skin SCC and BCC tumor cell proliferation and angiogenesis relationship in skin cancer occurs role in the development of clinical reasonable choice of surgical approach and prognostic provide valuable indicators. Materials and methods experimental material: skin SCC and BCC tissue samples of 51 cases, including of SCC28 cases, BCC23 cases. The SCC histological grade: Ⅰ 22 cases, 5 cases of grade Ⅱ, Ⅲ grade 1 cases. Material positions, respectively, from the scalp, face, extremities and perineum. 20 cases of normal skin tissue were taken from the remaining normal skin, beauty seeking normal skin, and other non-cancer patients with skin transplants are full thickness skin graft used as normal controls. 2 Methods: Immunohistochemical SP staining of HIF-1α, VEGF, PCNA and CD105 expression in skin SCC and BCC, and calculate the value of PI and MVD. All data are SPSS11.0 software package for statistical analysis. Test α = 0.05, P <0.05 for the difference was significant. Χ ~ 2 split further α = 0.0167. Results 1 HIF-1α protein expression of HIF-1α protein is expressed mainly in the cytoplasm or the nucleus of the tumor cells, the nucleus is more common in the edge of the cancer nests and tumor necrosis some strong expression, part of the stromal vascular endothelial cells also visible expression. HIF-1α protein in SCC positive expression rate was 82.14% (23/28), the BCC positive expression rate was 47.82% (11/23), HIF-1α protein in the epithelial cells of normal skin were negative (0 / 20). SCC and BCC, normal control group compared to the differences were statistically significant (P <0.0167); BCC and normal control group, the difference was statistically significant (P <0.0167). HIF-1α in well-differentiated SCC tissue positive expression rate of 77.27% (17/22), poorly differentiated SCC tissue positive expression rate was 100% (6/6), the positive expression rate of SCC degree of differentiation None significant correlation (P> 0.05). The the 2 VEGF protein expression of VEGF protein expression in the parenchymal cells of the tumor, the cells above the basal layer of the epidermis, the part of the vascular endothelial cells, outer root sheath cells visible weak expression, which the tumor parenchyma cells were stained darker, highly expressed in tumor cells next neovascularization VEGF. VEGF protein in the SCC, the positive expression rate was 67.85% (19/28), BCC positive expression rate of 30.43% (7/23), the epithelial cells of normal skin positive expression rate of 20.00% (4/20). SCC and BCC, normal control group compared the difference was statistically significant (P <0.0167); BCC and normal control group, the difference is not statistically significant (P> 0.05). VEGF in well-differentiated SCC tissue positive expression rate was 63.64% (14/22), in poorly differentiated SCC tissue positive expression rate was 83.33% (5/6), the positive rate and the degree of SCC differentiation was no significant correlation sex (P> 0.05). 3 CD105 protein expression of CD105 protein expression of vascular endothelial cells in cancer nests around interstitial membrane or cytoplasm, brownish yellow granules. CD105 in skin SCC, BCC and normal skin MVD values ??were 14.87 ± 3.48,9.18 ± 3.26 and 0.65 ± 0.43. SCC and the BCC and normal skin compared, the differences were statistically significant (P <0.05), BCC and normal skin compared, the difference was statistically significant (P <0.05); HIF-1α expression positive group MVD is 14.20 ± 3.67, HIF-1α expression the negative groups MVD value of 8.53 ± 3.18, the difference was statistically significant (P <0.05); VEGF expression positive group MVD value of 15.16 ± 3.37, VEGF expression the negative groups MVD value of 9.34 ± 3.37 with a difference statistically significant (P <0.05). 4 PCNA protein expression the PCNA protein located in the nucleus, brownish yellow granules. PCNA in skin SCC, BCC and normal skin PI values ??were 69.71 ± 6.04,53.11 ± 5.32 and 20.12 ± 4.77. SCC with the BCC and normal skin compared, the differences were statistically significant (P <0.05), BCC and normal skin compared, the difference was statistically significant (P <0.05). HIF-1α expression positive group PI value of 65.76 ± 8.92, HIF-1α expression negative group PI value of 55.12 ± 8.55, and the difference was statistically significant (P <0.05). The expression of VEGF-positive group PI value of 66.96 ± 8.93, VEGF expression the negative group PI value of 57.28 ± 8.87, the difference was statistically significant (P <0.05). 5 correlation analysis of the correlation analysis show, skin SCC and BCC in HIF-1α expression and VEGF expression was positive related (r = 0.555, P <0.05), BCC Organization PI and MVD value was positively correlated (r = 0.533, P <0.01 PI and MVD) SCC tissue no significant correlation (r = 0.360, P> 0.05). Conclusion 1 HIF-1α overexpression in skin SCC and BCC tissues, HIF-1α expression and VEGF expression, MVD value, PI values ??were positively correlated, suggesting that HIF-1α expression and skin SCC and BCC in neovascularization and cell proliferation may in its occurrence and development process play an important role, is expected to be used as a skin SCC and BCC's one of the diagnostic indicators. 2 VEGF overexpression in skin SCC tissue positive expression value of MVD, PI values ??were higher than those with negative expression, prompting the skin SCC neovascularization and cell proliferation; VEGF expression compared with normal skin differences in BCC not statistically significant, the biological behavior may slow growth, and BCC rarely transfer; positive expression value of MVD, PI values ??were higher than those with negative expression reflects a certain extent the BCC still have general malignancy infiltration characteristics of growth and metastasis. Therefore, VEGF still can not be used as an effective indicator of the extent of the evil judge BCC. 3 HIF-1α expression and VEGF expression and MVD was positively correlated with the expression of VEGF but BCC MVD values ??higher than the normal skin with normal skin close, prompted not only by the skin SCC and BCC in HIF-1α promote angiogenesis, VEGF expression up generated by other non-VEGF pathway may also promote the formation of new blood vessels, in order to maintain and promote tumor growth and infiltration. 4 combined detection of skin SCC and BCC of HIF-1α expression, MVD value and PCNA index, help to understand the biological behavior of skin SCC and BCC, and guide clinical treatment and prognosis.

Relationship of HIF-1α, PCNA and VEGF with Microvascular Density in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma

Abstract

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