Malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is GLUT1 expression a major prognostic factor? A preliminary study

Our plain-English summary of Malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is GLUT1 expression a major prognostic factor? A preliminary study, by J. Hommell-Fontaine, S. Isaac, G. Passot, et al (Annals of Surgical Oncology, 2013).

The study

• Authors: J. Hommell-Fontaine, S. Isaac, G. Passot, E. Decullier, A. Traverse-Glehen, E. Cotte, B. You, F. Mohamed, F.N. Gilly, O. Glehen, F. Berger
• Journal: Annals of Surgical Oncology
• Published: 2013;20(12):3892-8
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare primary peritoneal malignancy. Its prognosis has been improved by an aggressive locoregional treatment combining extensive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic factors are currently poorly defined for this disease but are essential if treatment is to be standardized.

Methods: Twenty-eight patients with DMPM, who were considered preoperatively to be candidates for CRS and HIPEC between June 1998 and August 2010 at our institution, were selected for this study. Medical records and histopathological features were retrospectively reviewed and 24 clinical, histological, and immunohistochemical parameters were assessed for their association with overall survival by univariate and multivariate analyses.

Results: The following factors were significantly associated with overall survival by univariate analysis: predominant histological growth pattern in the epithelioid areas, nuclear grooves in the epithelioid areas, atypical mitoses, and calretinin and GLUT1 expression by immunohistochemistry in the epithelioid areas. Expression of the facilitative glucose transporter protein GLUT1 in the epithelioid areas was the only factor independently associated with overall survival by multivariate analysis.

Conclusions: GLUT1 expression appears to be an indicator of poor prognosis in DMPM. Standard histological classification of DMPM may not be adequate to select patients for aggressive locoregional treatments, such as CRS and HIPEC. Multicenter validation of the prognostic factors identified in this preliminary study is needed to refine patient selection for potential cure.

In plain English

This was a retrospective study from one French hospital, Centre Hospitalier Lyon Sud. It covered 28 patients with diffuse malignant peritoneal mesothelioma (a cancer of the abdominal lining) who were considered between June 1998 and August 2010 for extensive surgery plus heated chemotherapy delivered into the abdomen (HIPEC). The article does not discuss asbestos exposure. The authors tested 24 clinical, tissue and staining features for links with overall survival. Median follow-up was 34 months and median overall survival was 37 months. At last follow-up, 14 patients had died of the disease. None of the five clinical factors was significant. Five tissue and staining features were associated with survival when each was tested on its own. When they were analysed together, only GLUT1, a glucose-transporter protein, in the epithelioid tumor areas remained independently associated with survival (hazard ratio 21.48; 95% confidence interval 2.69 to 171.4). Patients whose tumors expressed GLUT1 had worse survival. The authors concluded that GLUT1 appears to predict prognosis. They cautioned that the study was small and exploratory and needs confirmation in a larger multicenter study.

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: Retrospective single-institution study of prognostic factors (review of medical records and tumor tissue), with univariate and multivariate survival analysis
• Who was studied: 28 patients with histologically proven diffuse malignant peritoneal mesothelioma who were considered candidates for cytoreductive surgery and HIPEC at Centre Hospitalier Lyon Sud (Pierre-Bénite, France) between June 1998 and August 2010. Three patients were excluded: two with peritoneal spread from pleural mesothelioma and one who died after surgery. CRS and HIPEC were performed in 25 of the 28.
• Exposure: Asbestos exposure was not studied. The factors examined were 24 clinical, histological and immunohistochemical features (including GLUT1, calretinin, Ki67, p16 and p27 staining), tested against overall survival.
• Main results:
  • For all 28 patients, median follow-up was 34 months (range 1 to 91 months) and median overall survival was 37 months.
  • At last follow-up, 10 patients were alive with no evidence of disease, 4 were alive with disease, and 14 had died of disease.
  • In univariate analysis, using a multiple-comparison P value threshold of 0.013, none of the five clinical factors (sex, age, Peritoneal Cancer Index, Gilly's score, completeness of cytoreduction) was significant.
  • In univariate analysis, better overall survival was associated with: a nonsolid predominant pattern in epithelioid areas (P = 0.008), nuclear grooves in epithelioid areas (P = 0.003), no atypical mitoses (P = 0.004), a calretinin score of 200 or more in epithelioid areas (P = 0.002), and absence of GLUT1 expression in epithelioid areas (P = 0.004).
  • GLUT1 expression in the epithelioid areas was found in 57% of the cases (16 of 28 in Table 3).
  • In multivariate analysis, absence of GLUT1 expression in epithelioid areas was the only factor independently associated with improved overall survival (hazard ratio 21.48; 95% confidence interval 2.69 to 171.4; P = 0.0038). In Table 3 this hazard ratio compares tumors with GLUT1 in 5% or more of cells against tumors under 5%.
  • Histological subtype (epithelioid, 22 patients, versus biphasic, 6 patients) did not correlate with overall survival in this series.
• The authors' conclusion: The authors concluded that GLUT1 expression appears to be an indicator of poor prognosis in diffuse malignant peritoneal mesothelioma. They said standard histological classification may not be adequate to select patients for CRS and HIPEC, and that the findings should be confirmed in a multicenter study.
• Limitations the authors state:
  • Many factors were tested and the statistical analysis was exploratory, so the authors said results should be interpreted with caution.
  • The sample size was small, which the authors said may explain why histological subtype did not correlate with survival.
  • The authors described the study as preliminary and said a larger multicenter study is needed to confirm the results and test whether the factors are reproducible.

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Cytoreductive Surgery, HIPEC, GLUT1, Prognosis, Overall Survival, Epithelioid, Calretinin.

Related studies

• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies — G. Passot, N. Bakrin, et al. (2014)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)
• Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin — A.U. Blackham, P. Shen, et al. (2010)

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