196 Abstracts/Lung Cancer 13 (1995) 185-232

Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb Hiyama K, Ishioka S, Shirotani Y, Inai K, Hiyama E, Murakami I et al. Second Department Internal Medicine, Hiroshima Universi@ School Medicine, Hiroshima, 734. Gncogene 1995;10:937-44.

In the two-stage model of controlling cellular senescence in cultured human fibroblasts, retinoblastoma (Rb) and ~53 proteins may be key factors regulating the mortality stage 1 mechanism. In addition, the critical loss of telomeric DNA due to the end-replication problem may result in the mortality stage 2 mechanism. Cells which acquire telomerase activity can overcome the M2 mechanism by stabilizing telomere length and thus become immortal (telomere hypothesis). At present it is known whether cellular immortality is a prerequisite for all human cancers. To investigate this question and the applicability of the two-stage model to human cancers, we analysed the relationship between alterations of telomere length and other genetic changes in lung cancer. Among 60 primary lung cancer tissues, telomere length alterations were observed in 16 tumors (26.7%) including 14 with short and two with elongated telomeres. Ten of them revealed allelic loss of both p53 and Rb genes, and remaining six showed no abnormalities in both genes. We propose that inactivation of both ~53 and Rb genes may promote cell divisions causing telomere shortening in lung cancer as in the hvo- stage model, while there may be another pathway to overcome both M 1 and M2 mechanisms, especially for adenocarcinoma.

Pathology

Small cell lung cancer after chemotherapy. Morphological results Junker K, Krapp D, Muller K-M. Institutfur Pathologic, Berufsgen. Kliniken Betgmannsheil, Universitatsklinik, Burkle-de-la-Camp-Platz I, D-44789 Bochum. Pathologe 1995;16:217-22.

Resection specimens of I4 patients with small cell bronchial carcinoma atter ncoadjuvant chemotherapy were processed histologically and graded according to a three-step regression grading system: grade I, no or only slight tumor regression; grade II, incomplete tumor regression; grade III, complete tumor regression without vital tumor tissue. In five patients with either no vital tumor tissue or only small tumor remnants in the resection samples, a typical sequence of central fresh tumor necrosis, foam cell rim, vascular granulation tissue and peripheral scar formation was seen, This morphological finding may be interpreted as a characteristic, but unspecific parameter of good response to preoperative chemotherapy. The presence of vital tumor rims surrounding the capillary bed with intermingled necrotic foci, however, argues in favor of spontaneous tumor regression, which is commonly observed in small cell lung cancer.

Immunohistochemical localization of cytochrome P450 2El in human pulmonary carcinoma and normal bronchial tissue Kivisto KT, Linder A, Friedel G, Beaune P, Belloc C, Kroemer H et al. Dr Margarete Fischer-Bosch-Institut, Klinische Pharmakologie. Auerbachstrasse 112, D-70376Stuttgart. Wrchows Arch 1995;426:243- 7.

Cytochrome P450 2El (CYPZEI) is a major xenobiotic-metabolizing enzyme but data concerning its extrahepatic expression are few. CYP2El can metabolically activate many procarcinogens and therefore its presence in the lung might play a role in bioactivation of procarcinogens, so we studied the expression and localization of CYP2EI in primary pulmonary carcinomas and surrounding normal bronchial tissue from 28 patients, Seromucous glands showed expression of CYP2El in 19

and bronchial epithelium in 18 of the 28 samples of normal bronchial tissue. Thirteen of the correspondingcases of primary pulmonary carcinoma showed staining for CYPZEl. In 11 of these 13 cases, CYPlEl was also present in normal bronchial tissue. There was no statistically significant difference in the expression of CYP2El between adenocarcinomas and squamous cell carcinomas, No association was observed between the expression of CYP2El in tumour tissue and normal bronchial tissue. However, there was a significant correlation between the expression of CYP2El in seromucous glands and bronchial epithelium (r = 0.61, P < 0.01) of normal tissue. We conclude that CYP2El can be present in both normal and neoplastic bronchial tissue.

Bcl-2 protein: A prognostic factor inversely correlated to p53 in non-small-cell lung cancer Fontanini G, Vlgnati S, Bigini D, Mussi A, Lucchi M, Angeletti CA et al. Institute o$Pathologv Universily ofPisa, 57 L‘ia Roma, 56126 Piss. Br J Cancer 1995;71:1003-7.

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortu- nately become insu&ient in the prognostic evaluation of this type of cancer. As ~53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and ~53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prog- nosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed me- tastasis during follow-up or died of metastatic disease (I’ = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in pa- tients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, ~53 protein accumulation was observed in tumours with meta- static nodal involvement (P = 0.02) or in patients who developed metasta- sis during follow-up (P = 0.01). although no correlation was found be- tween ~53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product ~53 (P = 0.01). Thus, a high proportion of NSCLCs express ~53 and Bcl-2 proteins and their expression may have prognostic importance.

Lymphoepithelioma-like carcinoma of the lung. Two cases diagnosed in Caucasian patients Ferrara G. Nappi 0. Servizio di Anatomio Patologica. Azienda Ospedaliera ‘Gaetano Rummo ‘, Ma dell jlngelo, I, 82100 Benevento. Tumori 1995;81: 144-7.

Lymphoepithelioma-like carcinoma is a non-nasopharyngeal undifferentiated carcinoma with prominent lymphoid infiltration. Ten eases arising in the lung have been reported so far; seven cases were diagnosed in Orientals, with the Epstein-Barr virus (EBV) genome demonstrated in neoplastic cells by in situ hybridization; the remaining three cases affected Caucasian patients and showed no evidence of hybridized viral genome. The present study describes two additional cases of lymphoepithelioma-like carcinoma of the lung in Caucasians, with reference to the differential diagnosis versus other thoraco- media&ml malignancies. The neoplastic nuclei, blastlike in appearance, together with the immunohistochemical profile of the neeplastic cells (positivity for cytokeratins, and negativity for CD antigens, SlOO protein, placental alkaline phosphatase, and neuroendocrine markers) represent the basic pathologic features of a lymphoepithelioma-like carcinoma and allow its recognition even on small bioptic fragments, in which the