Prognosis in malignant mesothelioma related to MIB 1 proliferation index and histological subtype

doi:10.1016/S0046-8177(98)90043-0

Human Pathology

Volume 29, Issue 3, March 1998, Pages 246-251

https://doi.org/10.1016/S0046-8177(98)90043-0 Get rights and content

Abstract

The aims of this study were to evaluate the use of the proliferation marker MIB 1 and histological subtype as indicators of prognosis in malignant mesothelioma. Sections from 41 cases of malignant mesothelioma were histologically subtyped on hematoxylin and eosin sections and stained immunohistochemically for the proliferation marker MIB 1. A proliferation index was derived and the results compared with patient survival data. A statistically significant difference was found between the survival of patients having a low and high MIB 1 index (P < .001). Patients with tumors having a low MIB 1 index lived significantly longer than those with a high MIB 1 index. Patients with the spindle cell histological subtype of malignant mesothelioma had significantly shorter survival times than those with the epithelioid or mixed tumors (P < .01). The MIB 1 proliferation index and histological tumor subtype are useful markers of prognosis in malignant mesothelioma.

References (35)

J Peto et al.
Continuing increase in mesothelioma mortality in Britain
Lancet
(1995)
R Walz et al.
Malignant pleural mesothelioma: Some aspects of epidemiology, differential diagnosis and prognosis
G Hillerdal
Malignant mesothelioma 1982: Review of 4710 published cases
Br J Dis Chest
(1983)
K Hoekman et al.
Well-differentiated papillary mesothelioma of the peritoneum
L Johansson et al.
Aspects of histopathologic subtype as a prognostic factor in 85 pleural mesotheliomas
Chest
(1996)
CA Veys
ABC of Work Related Disorders: Occupational Cancers
Br Med J
(1996)
AS Alberts et al.
Malignant pleural mesothelioma: A disease unaffected by current therapeutic maneuvers
J Clin Oncol
(1988)
D Branscheid et al.
Diagnostic and therapeutic strategy in malignant pleural mesothelioma
Eur J Cardiothoracic Surg
(1991)
J Schildge et al.
Prognostic factors in diffuse malignant mesothelioma of the pleura
Pneumologie
(1989)
C Boutin et al.
Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 2: Prognosis and staging
Cancer
(1993)

C Boutin et al.

Diagnosis and prognosis of malignant mesothelioma

Rev Pract

(1990)

G Hulks et al.

Malignant pleural mesothelioma in western Glasgow 1980-6

Thorax

(1989)

V De Pangher Manzini et al.

Prognostic factors of malignant mesothelioma of the pleura

Cancer

(1993)

G Martensson et al.

Diagnosis and prognosis in malignant mesothelioma: A prospective study

Eur J Respir Dis

(1984)

M Ramael et al.

Proliferation in malignant mesothelioma as determined by mitosis counts and immunoreactivity for proliferating cell nuclear antigen (PCNA)

J Pathol

(1994)

J Gerdes et al.

Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67

J Immunol

(1984)

OW Kamel et al.

Thymidine labelling index and Ki-67 growth fraction in lesions of the breast

Am J Pathol

(1989)

Cited by (51)

Malignant Pleural Mesothelioma—Does Ki67 Make the Grade?
2021, JTO Clinical and Research Reports
PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy
2014, Journal of Thoracic Oncology
Citation Excerpt :
Interestingly, we found an increased cleaved caspase-3 apoptotic index and a decreased Ki-67 proliferative index in postchemotherapy specimens. Consistent with four previous reports, we found a high proliferation index before chemotherapy to be associated with a worse prognosis.44–47 Notably, our Ki-67 expression median scores were in close alignment with the MPM reports by Beer et al.44 and Kadota et al.45
The prognostic significance of activity biomarkers within the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway was assessed in two independent cohorts of malignant pleural mesothelioma (MPM) patients uniformly treated with a multimodal approach. We specifically assessed expression signatures in a unique set of pre- and postchemotherapy tumor samples.
Biomarker expression was assessed in samples of two independent cohorts of 107 (cohort 1) and 46 (cohort 2) MPM cases uniformly treated with platinum-based induction chemotherapy followed by extrapleural pneumonectomy from two different institutions, assembled on tissue microarrays. Expression levels of phosphatase and tensin homologue (PTEN), phospho-mTOR, and p-S6 in addition to marker of proliferation (Ki-67) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry and correlated with overall survival (OAS) and progression-free survival (PFS). To assess PTEN genomic status, fluorescence in situ hybridization was performed.
Survival analysis showed that high p-S6 and Ki-67 expression in samples of treatment naïve patients of cohort 1 was associated with shorter PFS (p = 0.02 and p = 0.04, respectively). High Ki-67 expression after chemotherapy remained associated with shorter PFS (p = 0.03) and OAS (p = 0.02). Paired comparison of marker expression in samples before and after induction chemotherapy of cohort 1 revealed that decreased cytoplasmic PTEN and increased phospho-mTOR expression was associated with a worse OAS (p = 0.04 and p = 0.03, respectively).
These novel data reveal a prognostic significance of expression changes of PI3K/mTOR pathway components during induction chemotherapy if confirmed in other patient cohorts and support the growing evidence to target the PI3K/mTOR pathway in the treatment of MPM.
Pericardial tumors
2008, Seminars in Diagnostic Pathology
Citation Excerpt :
Immunohistochemical studies of MPM have found that these tumors may be positive for a variety of antigens, including cytokeratin (CK), vimentin, epithelial membrane antigen (EMA), surfactant apoprotein (SP-A), epithelial antigen, thyroid transcription factor (TTF), thrombomodulin (TM), mesothelial cells, calretinin, and KI-67.20 Although KI-67 can be used to identify prognosis in patients with pleural malignant mesothelioma,21 a study by Hirano and coworkers found no significant difference in patients with MPM. Because their study consisted of three patients and all patients died within a year of diagnosis,20 it is important that immunohistochemical studies be done and analyzed so as to identify future predictors of poor prognosis.
A localized pleural based mass with intense uptake on positron emission tomography scan
2007, Chest
Citation Excerpt :
Although not pathognomonic, an immunohistochemical profile that is positive for calretinin, keratin, thrombomodulin, and vimentin, and is negative for CEA, SP-A, and CD15, the markers for adenocarcinoma, is highly suggestive of the mesothelial origin of the cells.1,24,26 Some authors have suggested that the proliferation index of67Ki should be part of the pathology report, as it was found to have an important prognostic value.30–33 The characteristic appearance of mesothelial cells on electron microscopy (ie, numerous long, slender, and smooth microvilli) point to the diagnosis of mesothelioma.1,3,29
Cell proliferation rate and telomerase activity in the differential diagnosis between benign and malignant mesothelial proliferations
2006, Pathology
The differential diagnosis of malignant mesothelioma (MM) from benign mesothelial lesions (BML) based on histopathological criteria is sometimes not satisfying and causes diagnostic problems for histopathologists. We aimed to investigate whether the immunohistochemically determined cell proliferation rate and telomerase activity, using Ki-67 and human telomerase reverse transcriptase (hTERT) immunohistochemistry, respectively, are useful in the differential diagnosis of MM from BML.
Sixty-six cases of MM (33 epithelioid, 30 biphasic and 3 sarcomatoid) and 22 cases of BML (15 reactive mesothelial proliferations and 7 fibrous pleuritis/pericarditis) were included in this study. We evaluated the proliferative activity by Ki-67 and telomerase activity by hTERT immuno-histochemistries for each case.
The mean value of the Ki-67 proliferation index (PI) in MMs was significantly higher than that of BMLs. Biphasic MMs have higher a Ki-67 PI than epithelioid and sarcomatoid types. Ki-67 immunohistochemistry has a sensitivity of 74%, specificity of 86% and positive predictive value of 94% in detecting MM. hTERT immunohistochemistry detected MM with sensitivity and specificity of 68%.
As a result, being cheap and simple methods, Ki-67 and hTERT immunohistochemistries can be used in differentiating malignant and benign mesothelial lesions in routine formalin-fixed, paraffin-embedded material.
Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers
2004, Modern Pathology
Diffuse malignant mesothelioma of the peritoneum is a rare diagnosis. Despite many histopathologic similarities between peritoneal and pleural tumors, clinical and prognostic features may be quite different. There is a paucity of data evaluating molecular features of peritoneal mesotheliomas. Therefore, we compared the results of a battery of immunohistochemical markers, some with therapeutic implications, in patients with primary peritoneal or pleural mesotheliomas. We examined 24 peritoneal and nine pleural malignant mesotheliomas with a battery of immunohistochemical markers (cytokeratin AE1/3, calretinin, c-kit/CD117, desmin, epidermal growth factor receptor (EGFR), estrogen receptors (ER), progesterone receptors (PR), MIB-1, and cleaved caspase-3) in an attempt to distinguish any differences in this tumor arising in these two distinct locations. The results indicate that the only marker to show a significant difference in its staining pattern between these two sites was EGFR (P=0.0004). In all, 92% (22/24) of peritoneal tumors demonstrated 3+ or 4+ immunoreactivity with EGFR, opposed to only 33% (3/9) pleural tumors. There was no significant difference in immunoreactivity between the pleural and peritoneal tumors with c-kit, ER, PR, cleaved caspase 3, calretinin, and desmin. There was a trend toward increased cytokeratin (P=0.07) and MIB-1 (P=0.08) expression in the peritoneal group. There was no significant difference in age, sex, or histologic subtype between the two locations. In conclusion, despite similarities between peritoneal and pleural mesothelioma, there are differences between this neoplasm arising in these two sites. The EGFR expression is more pronounced in peritoneal tumors compared to pleural tumors. The increased expression of EGFR in the peritoneal lesions may be of clinical significance with the recent emergence of epidermal growth factor receptor-targeted therapies.

View all citing articles on Scopus

View full text

Original contributionPrognosis in malignant mesothelioma related to MIB 1 proliferation index and histological subtype

Abstract

Lancet

Br J Dis Chest

Chest

ABC of Work Related Disorders: Occupational Cancers

Br Med J

Malignant pleural mesothelioma: A disease unaffected by current therapeutic maneuvers

J Clin Oncol

Diagnostic and therapeutic strategy in malignant pleural mesothelioma

Eur J Cardiothoracic Surg

Prognostic factors in diffuse malignant mesothelioma of the pleura

Pneumologie

Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 2: Prognosis and staging

Cancer

Diagnosis and prognosis of malignant mesothelioma

Rev Pract

Malignant pleural mesothelioma in western Glasgow 1980-6

Thorax

Prognostic factors of malignant mesothelioma of the pleura

Cancer

Diagnosis and prognosis in malignant mesothelioma: A prospective study

Eur J Respir Dis

Proliferation in malignant mesothelioma as determined by mitosis counts and immunoreactivity for proliferating cell nuclear antigen (PCNA)

J Pathol

Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67

J Immunol

Thymidine labelling index and Ki-67 growth fraction in lesions of the breast

Am J Pathol

Original contribution
Prognosis in malignant mesothelioma related to MIB 1 proliferation index and histological subtype