Expression of the 67 kDa laminin receptor and the α6 integrin subunit in serous ovarian carcinoma
Expression of the 67 kDa laminin receptor and the α6 integrin subunit in serous ovarian carcinoma
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DOI：
10.1023/a:1027340208536
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Reich, R
中科院分区：
文献类型：
--
作者：
Givant-Horwitz, V;Davidson, B;Reich, R
本研究的目的是分析67 kDa层粘连蛋白受体(LBP)前体和α6整合素亚单位两种层粘连蛋白受体在浆液性卵巢癌患者胸腔积液和实体瘤中的表达，并评价其预测作用。应用原位杂交技术检测88例积液和116例原发癌(=41例)和转移性(=75例)卵巢癌中上述mRNAs的表达。应用免疫组织化学方法检测24例积液和43例实体瘤中LBP蛋白的表达。应用流式细胞术(FCM)检测27例胸腔积液中α6整合素亚单位蛋白的表达。LBP mRNA在实体瘤的癌细胞(92/116例，79%)和间质细胞(9/116例，68%)中均有表达。积液中癌细胞的表达仍较高(88例中85例，占96%)。相反，在实体瘤(33/116；癌细胞28%，癌细胞23/116；间质细胞20%)和积液(36/88；41%)中，α6整合素亚基的检测频率都较低。LBP蛋白在24例胸腔积液中表达19例(79%)，在43例实体瘤中表达40例(93%)，且在术前接受化疗的胸腔积液中表达较高(P=0.024)。FCM显示27例胸腔积液中有17例(63%)有α6整合素亚单位的蛋白表达。FIGO IV期实体瘤中α6整合素亚单位基因的表达显著低于III期患者(P=0.004)，单因素分析显示α6整合素亚单位缺失预示患者总生存期(OS)显著缩短(P=0.018)。用流式细胞术预测a6整合素亚单位蛋白表达缺失的患者的中位OS为12个月，而表达该蛋白的肿瘤患者的中位OS为26个月，尽管这一发现没有达到显著意义(P=0.27)。总而言之，与以前的报道相反，与实体瘤相比，积液中α6整合素亚单位的mRNA和蛋白表达似乎并未下调。α6整合素亚单位mRNA(可能还有蛋白)表达缺失是晚期卵巢癌新的预后指标。LBP mRNA和蛋白在卵巢浆液性癌实体瘤和积液中的表达与α6整合素亚基无关。
The aim of this study was to analyze the expression of two laminin receptors, the 67kDa laminin receptor (LBP) precursor and the alpha6 integrin subunit, in effusions and solid tumors of patients diagnosed with serous ovarian carcinoma and to evaluate their predictive role. Eighty-eight effusions and one hundred sixteen primary (= forty-one) and metastatic (= seventy-five) ovarian carcinomas were evaluated for expression of the above-mentioned mRNAs using in situ hybridization (ISH). LBP protein expression was studied in 24 effusions and 43 solid tumors using immunohistochemistry (IHC). alpha6 integrin subunit protein expression was studied in 27 effusions using flow cytometry (FCM). Expression of LBP mRNA was frequently detected in both carcinoma (92 of 116 cases, 79%) and stromal (9 of 116 cases, 68%) cells in solid tumors. Expression was still higher in cancer cells in effusions (85 of 88 specimens, 96%). In contrast, alpha6 integrin subunit was less frequently detected in both solid tumors (33 of 116; 28% in carcinoma cells, 23 of 116; 20% in stromal cells) and effusions (36 of 88; 41%). LBP protein expression was found in 19 of 24 (79%) effusions and 40 of 43 (93%) solid tumors, and was higher in effusions of patients who received chemotherapy prior to tapping (P = 0.024). FCM showed protein expression of the alpha6 integrin subunit in 17 of 27 (63%) effusions. Expression of the alpha6 integrin subunit mRNA in tumor cells of solid lesions was significantly lower in solid tumors of FIGO stage-IV patients compared to those of patients diagnosed with stage-III-disease (P = 0.004), and its absence predicted significantly shorter overall survival (OS) in univariate analysis (P = 0.018). Absence of a6 integrin subunit protein expression using FCM predicted median OS of 12 months compared to 26 months for patients with tumors expressing the protein, although this finding did not reach significance (P = 0.27). In conclusion, as opposed to previous reports, both mRNA and protein expression of the alpha6 integrin subunit do not appear to be down-regulated in effusions compared to solid tumors. Loss of alpha6 integrin subunit mRNA ( and possibly protein) expression is a novel prognostic marker in advanced-stage ovarian carcinoma. LBP mRNA and protein expression is independent of that of the alpha6 integrin subunit in both solid tumors and effusions of serous ovarian carcinoma.