Osteopontin, GLUT1 and Ki-67 expression in malignant peritoneal mesothelioma: prognostic implications

Our plain-English summary of Osteopontin, GLUT1 and Ki-67 expression in malignant peritoneal mesothelioma: prognostic implications, by Y. Liu, G. Zheng, D. Yang, et al (Internal Medicine Journal, 2021).

The study

• Authors: Y. Liu, G. Zheng, D. Yang, X. Guo, L. Tian, H. Song, Y. Liang
• Journal: Internal Medicine Journal
• Published: 2021;51(6):896-904
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant peritoneal mesothelioma is the most common primary peritoneal neoplasm. The only universally recognised pathological prognostic factor is histopathological subtype. Prognostic markers based on patient features and clinical stages have been disappointing.

Aims: To assess the prognostic role of several clinicopathological features in a retrospective cohort of 60 patients diagnosed with peritoneal mesothelioma.

Methods: Sixty patients were centrally collected and were immunohistochemically analysed for the expression of osteopontin (OPN), GLUT1 and Ki-67. Labelling was assessed by two pathologists. Complete clinical information and follow-up were obtained from patients' records.

Results: OPN expression was identified in 52 (86.6%) of 60 specimens, and GLUT1 in 39 (65%) of 60 specimens. Univariate Cox regression analysis showed that a lower peritoneal carcinomatosis index (PCI), tumour-directed treatment (chemotherapy or surgery alone or in any combination), lower Ki-67, GLUT1 and lower OPN expression had a statistically significant positive effect on overall survival (OS). PCI (hazard ratio (HR) = 1.032 (95% confidence interval (CI): 1.000-1.067); P = 0.054) and tumour-directed treatment (HR = 0.211 (95% CI: 0.104-0.430); P < 0.001), Ki-67 (HR = 22.326 (95% CI: 3.523-141.498); P = 0.003) and OPN (HR = 7.268 (95% CI: 1.771-29.811); P = 0.009) retained independent prognostic significance in the multivariate analysis, all with a positive effect on OS with the exception of GLUT1.

Conclusions: OPN, Ki-67, treatment and PCI were independent indicators for OS, and a higher level of OPN expression correlated significantly with poorer OS.

© 2020 Royal Australasian College of Physicians.

In plain English

This retrospective study examined 60 patients with malignant peritoneal mesothelioma, an abdominal-lining cancer, diagnosed at Cangzhou Central Hospital, China, in 2012 to 2018. Asbestos exposure was documented for 52 patients: 35 through work and 17 environmentally. Fiber types were not named. The authors stained stored tumours for osteopontin (OPN), GLUT1 and Ki-67 and compared results with survival. Median survival was 6 months. OPN was found in 52 of 60 tumours, GLUT1 in 39. In the combined analysis, grade 3+ OPN staining versus negative staining had a hazard ratio of 7.268 (95% CI 1.771 to 29.811). Ki-67's hazard ratio was 22.326 (95% CI 3.523 to 141.498); its unit was not explained. Compared with best supportive care, tumour-directed treatment had a hazard ratio of 0.211 (95% CI 0.104 to 0.430), an association with a lower risk of death. The authors counted tumour extent (PCI) as independent despite a P value of 0.054, above their 0.05 cut-off. GLUT1 was not independent, and documented asbestos exposure was not significantly linked to survival. The authors concluded that higher OPN expression correlated with poorer survival and called for larger, prospective studies.

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 cohort study at a single hospital, using immunohistochemical staining of archived tumour tissue and Cox regression survival analysis
• Who was studied: 60 patients (22 male, 38 female; median age 62, range 42 to 84) diagnosed with malignant peritoneal mesothelioma at Cangzhou Central Hospital, Hebei, China, from October 2012 to October 2018; 30 epithelioid and 30 non-epithelioid
• Exposure: The study measured tumour expression of osteopontin (OPN), GLUT1 and Ki-67. Asbestos exposure, taken from medical records, was documented for 52 of 60 patients (35 occupational, 17 environmental). No fiber type is named. The discussion mentions women in the area working in handspun asbestos processes.
• Main results:
  • OPN was expressed in 52 of 60 tumour specimens (86.6%) and GLUT1 in 39 of 60 (65%); Ki-67 was expressed in all specimens
  • Median overall survival for the 60 patients was 6 months (range 1 to 48 months)
  • In multivariate analysis, OPN had a hazard ratio of 7.268 (95% CI 1.771 to 29.811), P = 0.009. Table 5 lists this figure for the 3+ staining grade compared with negative (grade 0) staining. Higher OPN was associated with poorer survival.
  • In multivariate analysis, Ki-67 had a hazard ratio of 22.326 (95% CI 3.523 to 141.498), P = 0.003. The article does not state the unit of comparison used in the model. Lower Ki-67 was associated with better survival.
  • In multivariate analysis, tumour-directed treatment (chemotherapy or surgery) compared with best supportive care had a hazard ratio of 0.211 (95% CI 0.104 to 0.430), P less than 0.001. This is an association with a lower hazard of death. The untreated patients were mostly untreated because of comorbidities, advanced stage or poor performance status.
  • In multivariate analysis, the peritoneal carcinomatosis index (PCI, a measure of tumour extent) had a hazard ratio of 1.032 (95% CI 1.000 to 1.067), P = 0.054. The authors counted it as independent, although they had set statistical significance at 0.05.
  • In univariate analysis, documented asbestos exposure (yes vs no) was not significantly associated with survival: hazard ratio 0.957 (95% CI 0.429 to 2.135), P = 0.915
  • GLUT1 expression was not associated with survival in the multivariate analysis
  • OPN expression was correlated with PCI (tumour extent), r = 0.267, P less than 0.05
• The authors' conclusion: The authors concluded that OPN, Ki-67, treatment and PCI were independent indicators of overall survival, and that higher OPN expression correlated significantly with poorer survival. They suggested GLUT1 may help in differential diagnosis but was not an independent survival indicator.
• Limitations the authors state:
  • Only 2 patients had cytoreductive surgery
  • A larger sample size is needed in further studies
  • The role of OPN in distinguishing tumour stage needs to be tested in a prospective study

Topics

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

Medical terms in this study, explained in our Lexicon: Osteopontin, GLUT1, Ki-67, Peritoneal Mesothelioma, Neoplasm, Chemotherapy, Overall Survival, Hazard Ratio.

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