A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma

Our plain-English summary of A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma, by K. Kadota, K. Suzuki, C. Colovos, et al (Modern Pathology, 2012).

The study

• Authors: K. Kadota, K. Suzuki, C. Colovos, C.S. Sima, V.W. Rusch, W.D. Travis, P.S. Adusumilli
• Journal: Modern Pathology
• Published: 2012;25(2):260-71
• Cited by: 128 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. MIB-1 immunohistochemistry was performed using tissue microarray, and MIB-1 labeling index was recorded as the percentage of positive tumor cells. Median overall survival of all patients was 16 months and correlated with nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitoses (P<0.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=0.012) and mitotic count (P<0.001) as independent prognostic factors, and these two factors were utilized to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107, median overall survival=28 months), grade II (n=91, 14 months), and grade III (n=34, 5 months). Not only was nuclear grade an independent predictor of overall survival (P<0.001), but it was also a stronger discriminator of survival than all currently available factors. Furthermore, nuclear grade was associated with time to recurrence (P=0.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<0.001) and nuclear atypia (P=0.037) and stratified overall survival (P<0.001) and time to recurrence (P=0.048), confirming the prognostic value of the nuclear grade. Nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than currently available clinicopathologic factors.

In plain English

Researchers at Memorial Sloan-Kettering Cancer Center in New York reviewed tissue slides from 232 patients diagnosed with epithelioid diffuse malignant pleural mesothelioma between 1989 and 2009. The study did not look at asbestos exposure. Seven nuclear features were scored. Median overall survival was 16 months. Two features independently predicted survival: nuclear atypia (how abnormal the nuclei looked) and mitotic count (how many cells were dividing). The authors combined them into a three-level nuclear grade. Median survival was 28 months for grade I (107 patients), 14 months for grade II (91 patients) and 5 months for grade III (34 patients). After accounting for other factors, the hazard ratio was 2.11 (95% confidence interval 1.52 to 2.94) for grade II versus I and 4.16 (2.47 to 7.03) for grade III versus II. Among 159 patients whose tumor was completely removed, median time to recurrence was 16 months for grade II and 37 months for grade I. The authors concluded that nuclear grading is a simple, practical, cost-effective tool that sorts patients by outcome and time to recurrence better than available factors.

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 pathologic review of tumor slides from a single-institution series of patients, with survival analysis
• Who was studied: 232 patients with epithelioid diffuse malignant pleural mesothelioma diagnosed between 1989 and 2009 at Memorial Sloan-Kettering Cancer Center, New York. Median age was 64 years (range 29 to 85) and 72% were male. By stage: 14 stage I, 54 stage II, 130 stage III and 34 stage IV.
• Exposure: Not an exposure study. Asbestos exposure was not measured or reported for these patients. The study examined microscopic features of tumor cell nuclei (nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, atypical mitoses) and MIB-1 labeling index.
• Main results:
  • Among all 232 patients, median overall survival was 16 months, 2-year overall survival was 34% and 5-year overall survival was 11%.
  • In multivariate analysis of nuclear features, severe versus mild nuclear atypia had a hazard ratio of 1.89 (95% CI 1.15 to 3.10, P = 0.012).
  • In the same analysis, high versus low mitotic count had a hazard ratio of 2.79 (95% CI 1.69 to 4.59, P less than 0.001).
  • Median overall survival by nuclear grade was 5 months for grade III (n=34), 14 months for grade II (n=91) and 28 months for grade I (n=107), P less than 0.001.
  • In multivariate analysis of overall survival including other prognostic factors, grade II versus grade I had a hazard ratio of 2.11 (95% CI 1.52 to 2.94), and grade III versus grade II had a hazard ratio of 4.16 (95% CI 2.47 to 7.03), both P less than 0.001.
  • The survival differences by grade were also seen in the 68 stage I to II patients and the 130 stage III patients.
  • Among 159 patients with complete resection, median time to recurrence was 16 months for grade II (n=69) and 37 months for grade I (n=68). The median was not reached for grade III (n=22). P = 0.004.
  • After excluding 34 pleomorphic cases, the findings remained significant in the remaining 198 patients. Median survival was 5 months for grade III (n=9), 13 months for grade II (n=82) and 28 months for grade I (n=107).
  • Of 158 cases tested for MIB-1, patients with a high MIB-1 labeling index (n=88) had a median overall survival of 12 months, compared with 23 months for those with a low index (n=70), P less than 0.001.
• The authors' conclusion: The authors concluded that nuclear grading in epithelioid mesothelioma is a simple, practical and cost-effective prognostic tool. In their view, it stratifies clinical outcome and time to recurrence better than currently available clinicopathologic factors.

Topics

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

Medical terms in this study, explained in our Lexicon: Nuclear Grading, Pleural Mesothelioma, Epithelioid, Mesothelioma, Staging, Nuclear Atypia, Mitotic Count, Immunohistochemistry.

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