TY - JOUR
T1 - Expression of the 67 kDa laminin receptor and the α6 integrin subunit in serous ovarian carcinoma
AU - Givant-Horwitz, Vered
AU - Davidson, Ben
AU - Van De Putte, Gregg
AU - Dong, Hiep Phuc
AU - Goldberg, Iris
AU - Amir, Sivan
AU - Kristensen, Gunnar B.
AU - Reich, Reuven
PY - 2003
Y1 - 2003
N2 - The aim of this study was to analyze the expression of two laminin receptors, the 67kDa laminin receptor (LBP) precursor and the α6 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). α6 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, α6 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 α6 integrin subunit in 17 of 27 (63%) effusions. Expression of the α6 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 α6 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 α6 integrin subunit do not appear to be down-regulated in effusions compared to solid tumors. Loss of α6 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 α6 integrin subunit in both solid tumors and effusions of serous ovarian carcinoma.
AB - The aim of this study was to analyze the expression of two laminin receptors, the 67kDa laminin receptor (LBP) precursor and the α6 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). α6 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, α6 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 α6 integrin subunit in 17 of 27 (63%) effusions. Expression of the α6 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 α6 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 α6 integrin subunit do not appear to be down-regulated in effusions compared to solid tumors. Loss of α6 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 α6 integrin subunit in both solid tumors and effusions of serous ovarian carcinoma.
KW - Integrins
KW - Laminin receptors
KW - Metastasis
KW - Prognosis
KW - mRNA in situ hybridization
UR - http://www.scopus.com/inward/record.url?scp=0344873647&partnerID=8YFLogxK
U2 - 10.1023/A:1027340208536
DO - 10.1023/A:1027340208536
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C2 - 14669791
AN - SCOPUS:0344873647
SN - 0262-0898
VL - 20
SP - 599
EP - 609
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 7
ER -