Faculty Bibliography

Spindle cell tumors that arise in or metastasize to the pleura must be thoroughly evaluated to arrive at a definitive diagnosis. Malignant mesothelioma is the most common tumor arising in the pleura, but metastatic tumors to the pleura occur more frequently. Additionally, many tumors arising in the lung and surrounding tissues involve the pleura. It is crucial to arrive at a correct diagnosis since many of these neoplasms show different prognoses and require varying treatment modalities. Sarcomatoid malignant mesothelioma is a rare tumor that arises in the pleura, and can be confused with numerous tumors arising in or metastasizing to the pleura, including synovial sarcoma, metastatic sarcomatoid carcinoma, metastatic melanoma, thymoma, renal cell carcinoma, localized fibrous tumor, leiomyosarcoma, and other types of sarcoma. Desmoplastic malignant mesothelioma is a fibrous sarcomatoid variant of malignant mesothelioma, and is occasionally mistaken for chronic fibrous pleurisy. Here, we review morphological, clinical, histological, immunohistochemical, ultrastructural, and molecular methods that aid in the diagnosis of spindle cell tumors of the pleura, and we provide specific examples of patients in which this multi-modal approach proved to be helpful

Maspin, a mammary homologue of Serine Protease Inhibitors, has been shown to inhibit tumor progression and metastasis. Recently, its biological functions have been linked to its subcellular localization. Specifically, a nuclear, opposed to a combined nuclear and cytoplasmic localization has been associated with increased survival in human malignancies, including non-small cell lung cancer (NSCLC). However, it is not known whether transformation affects maspin expression during lung carcinogenesis, and whether its subcellular localization correlates with the morphological features of NSCLC. To address these questions, we studied maspin expression in a model of transformation of bronchial epithelial cells and in resected NSCLC. We found that decreased maspin accompanied chemical transformation of normal immortalized bronchial epithelial cells BEAS 2B. Immunohistochemistry revealed maspin expression to be virtually universal in NSCLC, occurring in 72/77 Adenocarcinoma (ACa), and 46/46 squamous cell carcinoma (SqCCa). SqCCa showed almost exclusively a combined nuclear-cytosolic stain. In contrast, nuclear maspin, but not combined nuclear-cytoplasmic maspin significantly correlated with low histological grade, lower proliferative rate, absence of invasion, and negative p53 stain in ACa. These data support the hypothesis that nuclear localization of maspin may stratify subtypes of NSCLC with favorable clinical-pathological features

Simian virus 40 (SV40) has been detected in different human tumours in numerous laboratories. The detection of SV40 in human tumours has been linked to the administration of SV40-contaminated polio vaccines from 1954 until 1963. Many of these reports linked SV40 to human mesothelioma. Some studies have failed to detect SV40 in human tumours and this has caused a controversy. Here we review the current literature. Moreover, we present evidence showing how differences in the sensitivities of methodologies can lead to a very different interpretation of the same study. The same 20 mesothelioma specimens all tested negative, 2/20 tested positive or 7/20 tested positive for SV40 Tag by simply changing the detection method on the same immuno-precipitation/western blot membranes. These results provide a simple explanation for some of the apparent discordant results reported in the literature

PURPOSE: A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-alpha and ER-beta and the relationship between ER status, subject characteristics, and survival. EXPERIMENTAL DESIGN: Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-alpha and ER-beta expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status. RESULTS: Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-alpha. Nuclear ER-beta positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-beta-positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ER-beta-positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-beta-positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-beta-negative tumors. CONCLUSIONS: This study suggests differential expression by sex and influence on survival in men of nuclear ER-beta in lung cancer, particularly in adenocarcinomas