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DNA ploidy analysis of pleural mesotheliomas: its usefulness for their distinction from lung adenocarcinomas
1Division of Pathology, City of Hope National Medical Center, Duarte, California, USA.
Abstract:
The distinction of malignant mesotheliomas from adenocarcinomas with pleural involvement is often difficult, even with electron microscopic and state-of-the-art histochemical and immunologic studies. We evaluated the DNA ploidy and cell cycle of 45 clinically, morphologically, and immunohistochemically well-characterized malignant mesotheliomas to establish their ploidy profile and compared it with that of 41 pulmonary adenocarcinomas. All the cases were mucin negative and had been immunophenotyped with the following monoclonal antibodies: anti-keratin, anti-CEA, anti-Vimentin, anti-HMFG2, Leu M1 (CD15) and B72.3. Single cell suspensions from the paraffin blocks were prepared following Hedley's technique and were analyzed with a Coulter EPICS V flow cytometer. The resulting histograms were interpreted with the Multicycle software program. Five cases were excluded due to their high coefficients of variation. DNA aneuploidy was defined by the presence of more than one G0/G1 peak on the histograms obtained exclusively from the tumor sample. With this criterion, there is a possibility of missing aneuploid cases with a single aneuploid cycling population; however, fixatives and time of fixation produce such a remarkable variation in the fluorochrome uptake that any control, other than normal tissue present in the sample, was rendered unreliable. Five (14%) cases were DNA aneuploid with DNA indexes ranging from 1.2 to 1.9 (mean = 1.5). Three cases had increased S + G2/M values. Of the aneuploid cases, four were epithelial and one sarcomatous. In comparison, aneuploidy was found in 31 (75%) of the lung adenocarcinomas studied (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Malignant mesotheliomas are rarely DNA aneuploid (14%), unlike lung adenocarcinomas (75%). This DNA ploidy analysis aids in distinguishing these challenging pleural tumors.
Area of Science:
- Oncology
- Pathology
- Molecular Biology
Background:
- Distinguishing malignant mesothelioma from pleural adenocarcinoma is diagnostically challenging.
- Advanced techniques like immunohistochemistry are often insufficient for definitive differentiation.
Purpose of the Study:
- To evaluate DNA ploidy and cell cycle profiles of malignant mesotheliomas.
- To compare the DNA ploidy of malignant mesotheliomas with pulmonary adenocarcinomas.
Main Methods:
- Analysis of 45 malignant mesotheliomas and 41 lung adenocarcinomas using flow cytometry.
- DNA content and cell cycle analysis of single cell suspensions from paraffin-embedded tissues.
- Immunophenotyping using monoclonal antibodies including anti-keratin, anti-CEA, and B72.3.
Main Results:
- Only 14% of malignant mesotheliomas exhibited DNA aneuploidy, with DNA indexes ranging from 1.2 to 1.9.
- In contrast, 75% of pulmonary adenocarcinomas showed DNA aneuploidy (p < 0.0001).
- Three mesotheliomas had increased S + G2/M phase values; four aneuploid mesotheliomas were epithelial, one was sarcomatous.
Conclusions:
- DNA ploidy analysis demonstrates a significant difference between malignant mesothelioma and pulmonary adenocarcinoma.
- Lower rates of DNA aneuploidy in mesothelioma suggest it as a potential diagnostic marker to differentiate from adenocarcinoma.