Expression of the 67 kDa laminin receptor and the alpha6 integrin subunit in serous ovarian carcinoma.
The aim of this study was to analyze the expression of two laminin receptors, the 67 kDa 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 (79 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 alpha6 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.
Givant-Horwitz
Vered
V
Department of Pharmacology and Experimental Therapeutics, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Davidson
Ben
B
van de Putte
Gregg
G
Dong
Hiep Phuc
HP
Goldberg
Iris
I
Amir
Sivan
S
Kristensen
Gunnar B
GB
Reich
Reuven
R
D001202:Ascitic Fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D039503:Integrin alpha6 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010996:Pleural Effusion / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D017474:Receptors, Laminin / Q000378:metabolism*; D016019:Survival Analysis
D039503:Integrin alpha6; D012333:RNA, Messenger; D017474:Receptors, Laminin