Expression of the 67 kDa laminin receptor and the α6 integrin subunit in serous ovarian carcinoma

Vered Givant-Horwitz, Ben Davidson*, Gregg Van De Putte, Hiep Phuc Dong, Iris Goldberg, Sivan Amir, Gunnar B. Kristensen, Reuven Reich

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)599-609
Number of pages11
JournalClinical and Experimental Metastasis
Volume20
Issue number7
DOIs
StatePublished - 2003

Keywords

  • Integrins
  • Laminin receptors
  • Metastasis
  • Prognosis
  • mRNA in situ hybridization

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