Tumor/stromal caveolin-1 expression patterns in pleural mesothelioma define a subgroup of the epithelial histotype with poorer prognosis

Our plain-English summary of Tumor/stromal caveolin-1 expression patterns in pleural mesothelioma define a subgroup of the epithelial histotype with poorer prognosis, by L. Righi, M.C. Cavallo, G. Gatti, et al (American Journal of Clinical Pathology, 2014).

The study

• Authors: L. Righi, M.C. Cavallo, G. Gatti, V. Monica, I. Rapa, S. Busso, C. Albera, M. Volante, G.V. Scagliotti, M. Papotti
• Journal: American Journal of Clinical Pathology
• Published: 2014;141(6):816-27
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Malignant pleural mesothelioma (MPM) is a highly aggressive disease for which new prognostic biomarkers need to be identified. Caveolin-1 (CAV1), the most important member of caveolae, has been described as deregulated in MPM at the genomic level, but detailed histologic information on its distribution and prognostic role is still lacking.

Methods: A series of 131 MPMs (91 epithelial, 17 biphasic, and 23 sarcomatous histotype) were investigated for CAV1 expression with immunohistochemistry and correlated with clinical-pathologic variables and outcome.

Results: CAV1 was detected in neoplastic cells of 70 (77%) of 91 epithelial, 17 (100%) of 17 biphasic, and 23 (100%) of 23 sarcomatous MPMs. Furthermore, in the epithelial group, CAV1 expression in spindle-shaped stromal cells was detected in 61 (67%) of 91 cases.

Conclusions: The presence of stromal CAV1 expression was associated with a worse patient outcome. In MPM, CAV1 is differentially expressed according to low- to high-grade histotypes. Furthermore, in the MPM epithelial group, additional stromal CAV1 expression is associated with a worse prognosis.

Copyright© by the American Society for Clinical Pathology.

In plain English

This study examined caveolin-1 (CAV1), a cell-membrane protein, in tissue from 131 people with malignant pleural mesothelioma. They were diagnosed at San Luigi Hospital near Turin, Italy, between 1989 and 2010: 91 had epithelial, 17 biphasic and 23 sarcomatous tumors. The authors stained archived tumor samples for CAV1 and compared results with survival. CAV1 appeared in tumor cells in 70 of 91 epithelial cases (77%) and in all biphasic and sarcomatous cases, and levels differed significantly by tumor type. In 61 of 91 epithelial cases (67%), CAV1 also appeared in spindle-shaped cells of the surrounding supporting tissue (stroma). Among 54 epithelial cases treated with pemetrexed-based chemotherapy, stromal CAV1 was associated with worse prognosis (mean survival 17 months versus 37.8 months). Tumor-cell CAV1 showed no significant link to survival in the 63 pemetrexed-treated patients or in the epithelial cases of a second, independent series. Among those 37 epithelial cases, stromal CAV1-positive cases were more common in short-term survivors (under 24 months). The authors concluded that stromal CAV1 in epithelial mesothelioma is associated with worse prognosis, a finding they said needs further validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory pathology study of archived tumor tissue (immunohistochemistry for caveolin-1), correlated with clinical data and survival, plus tests on three mesothelioma cell lines
• Who was studied: 131 malignant pleural mesothelioma cases (93 men, 38 women; mean age 65; 91 epithelial, 17 biphasic, 23 sarcomatous), selected from a database of 630 cases diagnosed at San Luigi Hospital, Orbassano, Turin, Italy, between 1989 and 2010. The cases were split into a test series of 63 pemetrexed-treated cases (54 epithelial, 9 biphasic), a validation series of 45 cases (37 epithelial, 8 biphasic) and 23 sarcomatous cases. 40 pleuritis biopsies served as controls.
• Main results:
  • CAV1 was detected in tumor cells in 70 (77%) of 91 epithelial mesotheliomas.
  • All 23 sarcomatous mesotheliomas (100%) expressed CAV1 in tumor cells, at the highest levels. All 17 biphasic cases also expressed it. Tumor-cell CAV1 levels differed significantly across the three tumor types (P less than .0001).
  • CAV1 in stromal (supporting tissue) cells was detected in 61 (67%) of 91 epithelial cases.
  • In the 63 pemetrexed-treated patients, CAV1 in tumor cells had no significant prognostic role.
  • Among 54 pemetrexed-treated epithelial cases, stromal CAV1 was associated with worse prognosis: mean survival time 17 months vs 37.8 months, hazard ratio 0.27, confidence interval 0.14-0.5, P less than .0001.
  • Survival of epithelial cases with stromal CAV1 was comparable to that of biphasic mesothelioma.
  • In the 37 epithelial cases of the validation series, CAV1 in tumor cells did not play a prognostic role.
  • In the 37 epithelial cases of the validation series, more stromal CAV1-positive cases were found among short-term survivors (under 24 months) than among long-term survivors (P = .0002).
  • The biphasic-derived cell line (MSTO) had significantly higher CAV1 mRNA than the two epithelial-derived cell lines (REN and MPP89) (P = .02).
  • Some non-cancer pleuritis controls also showed stromal CAV1. Of 16 nonhyalinized chronic pleuritis cases, 4 were negative, 6 were weakly and focally positive, and 6 were positive.
• The authors' conclusion: The authors concluded that in epithelial pleural mesothelioma, additional stromal CAV1 expression is associated with a worse prognosis.
• Limitations the authors state:
  • The authors state that CAV1 as a marker of aggressive behavior needs further validation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Biomarker, Biphasic Mesothelioma, Immunohistochemistry.

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