整合素αv亚基在喉和下咽鳞状细胞癌中的表达及其与肿瘤血管发生的相关性

Expression of alpha-v integrin subunit in the laryngeal and hypopharyngeal squamons cell carcinomas and its relationship with tumor angiogenesis

目的探讨整合素αv亚基在喉和下咽鳞状细胞癌（简称鳞癌）组织中的表达及其临床意义，以及整合素αv亚基表达与肿瘤血管发生的相关性。方法设计制作喉和下咽鳞状细胞癌组织芯片，应用免疫组化技术在组织芯片上检测整合素αv亚基和CD105的表达，根据CD105表达计算肿瘤新生血管密度，分析整合素αv亚基表达与喉和下咽鳞癌侵袭转移的关系，以及整合素αv亚基表达与肿瘤新生血管密度的相关性。结果喉和下咽原发鳞癌组织中整合素αv亚基阳性表达率为68．0％（51／75），明显高于癌旁正常组织（10．3％，3／29，Х^2=28．68，P〈0．001）；淋巴转移癌中整合素αv亚基表达率达100．0％（20／20），明显高于原发癌（Х^2=12．69，P〈0．05）和癌旁正常组织（Х^2=38．77，P〈0．001）；有淋巴转移组表达率明显高于无淋巴转移组（Х^2=10．87，P〈0．001）；整合素αv亚基的表达与肿瘤新生血管密度有明显相关性，阳性表达组的肿瘤微血管密度明显高于弱阳性组（q=3．31，P〈0．05）和阴性组（q=6．61，P〈0．001）；整合素αv亚基的表达率按照肿瘤的原发部位、分化程度、浸润范围以及患者的年龄、性别分组，差异均无统计学意义（P值均〉0．05）。结论整合素αv亚基的表达与喉和下咽鳞癌的淋巴转移关系密切，其过量表达可能通过诱发微血管形成而导致肿瘤发生侵袭和转移，整合素αv亚基有可能成为临床预测喉癌和下咽癌淋巴转移趋势的新型标记物。

Objective To investigate the expression of integrin alpha-v subunit in laryngeal and hypopharyngeal squamous cell carcinomas （LHSCC） and to correlate the expression ratio with clinic and pathologic features of LHSCC, meanwhile, to investigate the relationship between the expression of integrin alpha-v subunit and tumor angiogenesis. Methods A tissue microarray of LHSCC was designed and made. Using this microarray, the expression of integrin alpha-v subunit in LHSCC was studied by immunohistochemistry, and the expression disparity in different clinic and pathologic staging of LHSCC was analyzed. The immunohistochemical staining of CD105 was done in the same microarray, the intratumor microvessel density （IMVD） was calculated by CD105 staining. The relationship between integrin alpha-v subunit expression and the IMVD was analyzed. Results In primary cancer tissue, the expression ratio of integrin alpha-v subunit was 68.0% （51/75）, significantly higher than normal tissue beside cancer （ 10. 3% ,3/29, Х^2 = 28.68, P 〈 0. 001 ） ; the expression ratio of integrin alpha-v subunit in lymph node metastatic carcinoma was 100. 00% （ 20/20 ） , significantly higher than normal tissue （ Х^2 = 38.77, P 〈 0. 001 ） and primary cancer tissue （Х^2 = 12. 69, P 〈 0. 05 ） ; in group with lymph node metastasis, the expression ratio of integrin alpha-v subunit was significantly higher than group without lymph node metastasis （Х^2= 10. 87, P 〈 0. 001 ） ; the IMVD of the group with integrin alpha-v subunit positive expression was significantly higher than the group with integrin alpha-v subunit negative expression （ P 〈 0. 001 ） . Conclusions There was significant relationship between integrin alpha-v subunit expression and lymphatic metastasis of LHSCC. Overexpression of the integrin alpha-v subunit may have contributed to the tumor angiogenesis and lead to lymphatic metastasis. Integrin alpha-v suhunit may become a novel lymphatic metastasis marker of LHSCC.