Loss of NPM2 expression is a potential immunohistochemical marker for malignant peritoneal mesothelioma: a single-center study of 92 cases

Our plain-English summary of Loss of NPM2 expression is a potential immunohistochemical marker for malignant peritoneal mesothelioma: a single-center study of 92 cases, by H.L. Wu, Z.R. Yang, Y.D. Su, et al (World Journal of Surgical Oncology, 2022).

The study

• Authors: H.L. Wu, Z.R. Yang, Y.D. Su, R. Ma, X.M. Du, Y. Gao, Y. Li
• Journal: World Journal of Surgical Oncology
• Published: 2022;20(1):350
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. In-depth pathological analysis is essential to assess tumor biological behaviors and explore potential therapeutic targets of MPM. Nucleoplasmin 2 (NPM2) is a molecular chaperone that binds histones and may play a key role in the development and progression of tumors. This study aimed to analyze the correlation between the expression level of NPM2 and the main clinicopathological characteristics and prognosis of MPM.

Methods: Ninety-two postoperative specimens from MPM patients following cytoreductive surgery were collected. Postoperative specimens were stained with immunohistochemistry. The expression level of NPM2 was quantitatively analyzed by QuPath-0.3.2 software. Univariate and multivariate analyses were conducted to investigate the correlation between NPM2 expression and other conventional clinicopathological characteristics.

Results: Among the 92 MPM patients, there were 47 males (48.9%) and 45 females (51.1%), with a median age of 56 (range: 24-73). There were 70 (76.0%) cases with loss of NPM2 protein expression, 11 (12.0%) cases with low expression, and 11 (12.0%) cases with high expression. Univariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was negatively correlated with the following three clinicopathological factors: completeness of cytoreduction (CC) score, vascular tumor emboli, and serious adverse events (SAEs) (all P < 0.05). Multivariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was independently negatively correlated with the following two clinicopathological factors: CC score [odds ratio (OR) = 0.317, 95% CI: 0.317-0.959, P = 0.042] and vascular tumor emboli (OR = 0.092, 95% CI = 0.011-0.770, P = 0.028). Survival analysis showed that loss of NPM2 protein expression (negative vs. positive) was associated with poor prognosis of MPM.

Conclusions: Loss of NPM2 expression is a potential immunohistochemical marker for MPM.

© 2022. The Author(s).

In plain English

This retrospective study from one hospital in Beijing, China, examined tumor tissue from 92 patients with malignant peritoneal mesothelioma, a cancer of the lining of the abdomen. All had cytoreductive surgery plus heated abdominal chemotherapy between May 2015 and October 2021. The article does not discuss asbestos exposure. The researchers stained the tissue for a protein called NPM2 and measured it with image-analysis software. NPM2 was absent in 70 of the 92 tumors (76.1%) and present in 22. Absence of NPM2 was associated with less complete removal of tumor at surgery and with tumor cells inside blood vessels, including in analyses adjusted for other factors. Patients without NPM2 had worse survival in a simple comparison (P = 0.046). However, NPM2 was not an independent predictor of survival once other factors were accounted for. A three-level grading of NPM2 (absent, low, high) was not linked to survival. The authors concluded that loss of NPM2 is a potential tissue-staining marker for this cancer. They noted that their sample was small and that a larger multicenter study is needed.

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-center study of tumor specimens, using immunohistochemistry (tissue staining) with software-based quantitative analysis
• Who was studied: 92 patients with malignant peritoneal mesothelioma (47 male, 45 female; median age 56, range 24 to 73; 75 epithelioid, 17 non-epithelioid) who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) at Beijing Shijitan Hospital, China, from May 2015 to October 2021 and had complete clinical data
• Exposure: Asbestos exposure is not addressed. The factor studied was expression of the protein NPM2 (nucleoplasmin 2) in tumor tissue. It was classed as negative (loss) or positive, and as negative, low or high, and compared with clinical and pathological features and survival.
• Main results:
  • Of the 92 patients, 22 (23.9%) were positive for NPM2 protein and 70 (76.1%) were negative. Of the 22 positive cases, 11 had high and 11 had low expression.
  • Where NPM2 was present, it was in the cytoplasm in 18 of 92 cases and in the nucleus in 4 of 92 cases.
  • In univariate analysis, NPM2 status (negative vs. positive) was negatively correlated with PCI score, CC score (completeness of cytoreduction), vascular tumor emboli and serious adverse events. In multivariate analysis it remained independently correlated with CC score (OR = 0.332, 95% CI 0.112 to 0.984, P = 0.047) and vascular tumor emboli (OR = 0.095, 95% CI 0.012 to 0.764, P = 0.027).
  • NPM2 expression level (negative vs. low vs. high) was independently negatively correlated with CC score (OR = 0.317, 95% CI as printed 0.317 to 0.959, P = 0.042) and with vascular tumor emboli (OR = 0.092, 95% CI 0.011 to 0.770, P = 0.028).
  • For all 92 patients, median follow-up was 46.9 months and median overall survival was 33.8 months (95% CI 23.6 to 44.0 months). 48 patients (52.2%) had died. Survival rates at 1, 2, 3 and 5 years were 90.0%, 64.4%, 49.2% and 41.0%.
  • In univariate survival analysis, NPM2 protein expression (negative vs. positive) was related to prognosis (P = 0.046). NPM2 expression level (negative, low, high) was not associated with prognosis (P > 0.05).
  • In multivariate survival analysis, NPM2 expression was not an independent prognostic factor. The independent factors were KPS, preoperative tumor markers, Ki-67, serious adverse events and red blood cell infusion.
• The authors' conclusion: The authors concluded that loss of NPM2 expression is a potential immunohistochemical marker for malignant peritoneal mesothelioma. They suggested NPM2 may be a tumor suppressor gene, and that its independent correlation with vascular tumor emboli indicates NPM2 could help evaluate the tumor's biological behavior.
• Limitations the authors state:
  • The sample size was small. The authors call for a larger multicenter study to clarify the clinical value of NPM2.
  • Because of small numbers, differences between nuclear and cytoplasmic NPM2 localization could not be analyzed.

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, Prognosis, Cytoreductive Surgery, Immunohistochemistry, Completeness of Cytoreduction (CC) Score, Multivariate Analysis, Odds Ratio.

Related studies

• Risk factors and prognosis of malignant peritoneal mesothelioma with paraneoplastic syndrome — X.L. Liang, Y.D. Su, et al. (2024)
• Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors — M. Miettinen, M.S. Rikala, et al. (2012)
• Analysis on the efficacy and safety of chemotherapy combined with or without bevacizumab after CRS+HIPEC in patients with malignant peritoneal mesothelioma: a single-center retrospective study — Z.R. Yang, X.L. Liang, et al. (2026)
• Evaluation of MTAP immunohistochemistry loss of expression in ovarian serous borderline tumors as a potential marker for prognosis and progression — N. Nilforoushan, N.A. Moatamed (2020)
• Prognostic associations of PD-L1 expression and BAP1 loss in pleural mesothelioma: a retrospective single-center cohort from Colombia — R. Brugés, C. Carvajal, et al. (2026)
• Feasibility and outcomes of cytoreductive surgery and HIPEC for peritoneal surface malignancies in low- and middle-income countries: a single-center experience of 232 cases — S. Deo, M. Ray, et al. (2021)

Browse more research in World Journal of Surgical Oncology, or return to medical research.