1
Abstracts/kg Gmcer 14 (19%) 377-408 significant trend toward increased survival was observed in BCLP( +) SCC cases (66 96 5-year survival in BCLP[ +] vs 43 46 in BCLP[-] [P = .l I]). Proportional hazards analysis failed to disclose significant independent risk factors. These data suggest that bcl-2 protein immunoreactivity has limited prognostic value in the pathological evaluation of NSCLC. Theexpression of trophoblasticcell markers by lung carcinomas Boucher LD, Yom& K. PathologyLaboratory Medicine SW. , Veterans Affairs Medical Center, 22SOLeestown Rd. Lexington, KY4051 I-1093. Hum Path01 1995;26:1201-6. The authors studied the expression of trophoblastic cell markers in lung carcinomas cells by immtmopetoxidase staining using antibodies againstthreetropboblasticglycoproteins(humanchorionicgonadotropin [hCG]; human placental lactogen ]h]PL]; pregnancy-specific 8,- glycoprotein [SP-I]). One hundred five tissue sections from 44 lung carcinomas of various histological types were examined for positive staining with three antibodies. Hematoxylin- rosin-stained sections from the same tissue blocks were examined for the presence of tumor giant cells. The aim was to study the relationship between tumor giant cells and die trophoblaatic glycoprotein expression in lung carcinomas. Small cell carcinoma (XC) did not show any positive reaction with all three markers. Squamous cell carcinoma (SQCC) showed positive staining with hCG in 21% of casea, hPL in 28%, and SP-1 in 64%. Adenocarcinoma showed positive staining with hCG in 60% of cases, hPL in IO%, and SP-1 in 80%. Large cell carcinoma (LCC) showed positive staining with hCG in 93% of cases, hPL in 56%, and SP-I in 93%. The positive reaction did not appear to be restricted to nor associated with the tumor giant cells. It was concluded that these trophoblastic cell markers are expressed in various types of lung carcinomas and that they are not associated with certain histological types or with tumor giant cells. In situ detection of Epstein-Barr virus in non-small cell lung carcinomas Wong MP, Chung LP, Yuen ST, Leung SY, Chart SY, Wang E et al. Department of Pathology, Queen Mary Hospital, PorgUkam Road, Hong Kong. J Pathol 1995;177:23340. Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and lymphoepithelioma-like carcinomas (LELC) of foregut- derived organs. Recently this group of EBV-associated carcinomas has been expanded by the identification of the virus in conventional adenocarcinomas of the stomach. In situ hybridization (ISH) using a sensitivedigoxigenin-IabelledEBER RNAprobewt~sperforn~don 167 consecutive unselected primary non-small cell lung carcinomas, to determine the frequency of EBV association in these tumours. Nine cases (5.4 per cent) showed strong EBER signals in the tumour cell nuclei. By immunohistochemistry, four of the EBER-positive tumours showed patchy expression of the viral latent membrane protein (LMP- 1) and none showed any expression of the EBV nuclear antigen 2 (EBNA2). Morphologically, all the positive turnouts were LELC, whereas no conventional type of non-small cell lung carcinoma showed EBV association. The LELC presented a morphological spectrum from undifferentiated to squamoid or glandular differentiation. The patients showed a male to female ratio of 8: 1. The mean age at presentation was 48 years. Smoking was not a risk factor. All patients were alive at follow-up periods of 23-52 months. Southern blot anaiysis performed on eight of the nine positive tumours showed a clonal episomal form of EBV, suggesting the clonal expansion of an infected tumour cell early in oncogenesis. These characteristics of the EBV-associated lung tumours justify their consideration as a distinct clinicopathological entity. Activation of the precursor of gelatinase A/72 kDa type IV eollagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT- MMP) and with lymph node metastasis Tokuraku M, Sato H, Murakami S, Okada Y, Watanabe Y, Seiki M. Dept. Molecular Virology/Oncology. Cancer Research Institute, Kanazawa University, Takara-machi 13-1, Kanazawa. Ishikawa 920. Int J Cancer 1995;64:355-9. We have identified a novel membrane-type matrix metalloproteinase (MT-MMP) expressed on the cell surface and inducing activation of pro gelatinase A in vitro. In this study, we further examined the possibility that MT-MMP is the activator of pro-gelatinam A in tumors as well as in vitro. Expression of MT-MMP mRNA was analyzed by Northern blotting in 58 cases of human lung carcinomas. MT-MMP mRNA expression was increased in tumor tissues compared with adjacent normal tissues. The ratio of MT-MMP mRNA levels in tumor/normal tissues(T/Nratio) was 3.19 it 1.62 in29casesofadenocarcinoma, 3.09 f 1.44 in 24 cases of squamous cell carcinoma, 4.40 f 0.47 in 3 cases of large cell carcinoma and 3.63 f 2.11 in 2 cases of small cell carcinoma, respectively. Activated gelatinase A, as detected by gelatin zymography, was also predominant in tumors compared with normal tissue counterparts, though the difference in mRNA levels was not significant. The activation ratio of gelatinase A in tumor vs. normal tissues correlated well with that of MT-MMP mRNA expression and with lymph node metastases. Our findings suggest that MT-MMP is indeedthetumor-specificactivatorofpro-gelatinase Am lungcarcinomas and is important to initiate invasion of basement membranes. ClinicalsignifIcanceorargyruphilicnucleolarorganizerregions (AgNOBs) in squamous cell carcinoma of the lung Han SB, Jean YJ, Lee SS. Depanment of Internal Medicine, Institute of Medical Science, Keimyung Univ. School of Medicine, Taegu. Tuberc Respir Dis 1995; 42:513-21. Background: Nucleolar organizer regions (NORs) are chromosomal segments encoding for ribosomal RNA and associated with argyrophilic nonhistone protein. Ribosomal RNA genes ultimately direct ribosome and protein synthesis, and it has been suggested the numbers of NORs detected in the cell may reflect nuclear and cellular activity. This study was performed to evaluate the applicability of AgNORs to the diagnosis of squamous cell carcinoma of the lung. Method: The one step silver methods (AgNORs) was used to stain NORs in the routinely processed, formalin fixed, paraffin embedded sections of 36 cases of squamous cell carcinoma of the lung obtained by surgical resection of primary tumor. In each specimen, 100 tumor cells and 100 normal cells adjacent to the tumor chosen at random were examined under an oil immersion lens at a magnification of x 1000. The mean number of AgNORs per nucleus was calculated for each specimen. Results: The mean number of AgNORs per nucleus (mAgNORs) of normal bronchial epithelium and squamous cell carcinomaof the lung was 1.74 + 0.25 and 4.05 * 0.80, respectively. The difference of mAgNOR between normal and tumor tissue was statistically significant (p < 0.001). Therewas no statistical differenceamong tumorsofdifferentstages. ThedifferenceofmAgNOR between normal and tumor tissue was statistically significant in each TNM stage (p < 0.05). Conclusion: Mean AgNOR count may be used as a useful marker for the differential diagnosis of benignancy and malignancy, and proliferative activity of the cell in squamous cell carcinoma of the lung. But there was no statistical difference in mean AgNOR count among tumors of different surgical stages. Further studies for the application of mAgNORs to the diagnosis of other histologic types and cytologic specimens of the lung cancer are needed.

The expression of trophoblastic cell markers by lung carcinomas

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Abstracts/kg Gmcer 14 (19%) 377-408

significant trend toward increased survival was observed in BCLP( +) SCC cases (66 96 5-year survival in BCLP[ +] vs 43 46 in BCLP[-] [P = .l I]). Proportional hazards analysis failed to disclose significant independent risk factors. These data suggest that bcl-2 protein immunoreactivity has limited prognostic value in the pathological evaluation of NSCLC.

Theexpression of trophoblasticcell markers by lung carcinomas Boucher LD, Yom& K. PathologyLaboratory Medicine SW. , Veterans Affairs Medical Center, 22SOLeestown Rd. Lexington, KY4051 I-1093. Hum Path01 1995;26:1201-6.

The authors studied the expression of trophoblastic cell markers in lung carcinomas cells by immtmopetoxidase staining using antibodies againstthreetropboblasticglycoproteins(humanchorionicgonadotropin [hCG]; human placental lactogen ]h]PL]; pregnancy-specific 8,- glycoprotein [SP-I]). One hundred five tissue sections from 44 lung carcinomas of various histological types were examined for positive staining with three antibodies. Hematoxylin- rosin-stained sections from the same tissue blocks were examined for the presence of tumor giant cells. The aim was to study the relationship between tumor giant cells and die trophoblaatic glycoprotein expression in lung carcinomas. Small cell carcinoma (XC) did not show any positive reaction with all three markers. Squamous cell carcinoma (SQCC) showed positive staining with hCG in 21% of casea, hPL in 28%, and SP-1 in 64%. Adenocarcinoma showed positive staining with hCG in 60% of cases, hPL in IO%, and SP-1 in 80%. Large cell carcinoma (LCC) showed positive staining with hCG in 93% of cases, hPL in 56%, and SP-I in 93%. The positive reaction did not appear to be restricted to nor associated with the tumor giant cells. It was concluded that these trophoblastic cell markers are expressed in various types of lung carcinomas and that they are not associated with certain histological types or with tumor giant cells.

In situ detection of Epstein-Barr virus in non-small cell lung carcinomas Wong MP, Chung LP, Yuen ST, Leung SY, Chart SY, Wang E et al. Department of Pathology, Queen Mary Hospital, PorgUkam Road, Hong Kong. J Pathol 1995;177:23340.

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and lymphoepithelioma-like carcinomas (LELC) of foregut- derived organs. Recently this group of EBV-associated carcinomas has been expanded by the identification of the virus in conventional adenocarcinomas of the stomach. In situ hybridization (ISH) using a sensitivedigoxigenin-IabelledEBER RNAprobewt~sperforn~don 167 consecutive unselected primary non-small cell lung carcinomas, to determine the frequency of EBV association in these tumours. Nine cases (5.4 per cent) showed strong EBER signals in the tumour cell nuclei. By immunohistochemistry, four of the EBER-positive tumours showed patchy expression of the viral latent membrane protein (LMP- 1) and none showed any expression of the EBV nuclear antigen 2 (EBNA2). Morphologically, all the positive turnouts were LELC, whereas no conventional type of non-small cell lung carcinoma showed EBV association. The LELC presented a morphological spectrum from undifferentiated to squamoid or glandular differentiation. The patients showed a male to female ratio of 8: 1. The mean age at presentation was 48 years. Smoking was not a risk factor. All patients were alive at follow-up periods of 23-52 months. Southern blot anaiysis performed on eight of the nine positive tumours showed a clonal episomal form of EBV, suggesting the clonal expansion of an infected tumour cell early in oncogenesis. These characteristics of the EBV-associated lung tumours justify their consideration as a distinct clinicopathological entity.

Activation of the precursor of gelatinase A/72 kDa type IV eollagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT- MMP) and with lymph node metastasis Tokuraku M, Sato H, Murakami S, Okada Y, Watanabe Y, Seiki M. Dept. Molecular Virology/Oncology. Cancer Research Institute, Kanazawa University, Takara-machi 13-1, Kanazawa. Ishikawa 920. Int J Cancer 1995;64:355-9.

We have identified a novel membrane-type matrix metalloproteinase (MT-MMP) expressed on the cell surface and inducing activation of pro gelatinase A in vitro. In this study, we further examined the possibility that MT-MMP is the activator of pro-gelatinam A in tumors as well as in vitro. Expression of MT-MMP mRNA was analyzed by Northern blotting in 58 cases of human lung carcinomas. MT-MMP mRNA expression was increased in tumor tissues compared with adjacent normal tissues. The ratio of MT-MMP mRNA levels in tumor/normal tissues(T/Nratio) was 3.19 it 1.62 in29casesofadenocarcinoma, 3.09 f 1.44 in 24 cases of squamous cell carcinoma, 4.40 f 0.47 in 3 cases of large cell carcinoma and 3.63 f 2.11 in 2 cases of small cell carcinoma, respectively. Activated gelatinase A, as detected by gelatin zymography, was also predominant in tumors compared with normal tissue counterparts, though the difference in mRNA levels was not significant. The activation ratio of gelatinase A in tumor vs. normal tissues correlated well with that of MT-MMP mRNA expression and with lymph node metastases. Our findings suggest that MT-MMP is indeedthetumor-specificactivatorofpro-gelatinase Am lungcarcinomas and is important to initiate invasion of basement membranes.

ClinicalsignifIcanceorargyruphilicnucleolarorganizerregions (AgNOBs) in squamous cell carcinoma of the lung Han SB, Jean YJ, Lee SS. Depanment of Internal Medicine, Institute of Medical Science, Keimyung Univ. School of Medicine, Taegu. Tuberc Respir Dis 1995; 42:513-21.

Background: Nucleolar organizer regions (NORs) are chromosomal segments encoding for ribosomal RNA and associated with argyrophilic nonhistone protein. Ribosomal RNA genes ultimately direct ribosome and protein synthesis, and it has been suggested the numbers of NORs detected in the cell may reflect nuclear and cellular activity. This study was performed to evaluate the applicability of AgNORs to the diagnosis of squamous cell carcinoma of the lung. Method: The one step silver methods (AgNORs) was used to stain NORs in the routinely processed, formalin fixed, paraffin embedded sections of 36 cases of squamous cell carcinoma of the lung obtained by surgical resection of primary tumor. In each specimen, 100 tumor cells and 100 normal cells adjacent to the tumor chosen at random were examined under an oil immersion lens at a magnification of x 1000. The mean number of AgNORs per nucleus was calculated for each specimen. Results: The mean number of AgNORs per nucleus (mAgNORs) of normal bronchial epithelium and squamous cell carcinomaof the lung was 1.74 + 0.25 and 4.05 * 0.80, respectively. The difference of mAgNOR between normal and tumor tissue was statistically significant (p < 0.001). Therewas no statistical differenceamong tumorsofdifferentstages. ThedifferenceofmAgNOR between normal and tumor tissue was statistically significant in each TNM stage (p < 0.05). Conclusion: Mean AgNOR count may be used as a useful marker for the differential diagnosis of benignancy and malignancy, and proliferative activity of the cell in squamous cell carcinoma of the lung. But there was no statistical difference in mean AgNOR count among tumors of different surgical stages. Further studies for the application of mAgNORs to the diagnosis of other histologic types and cytologic specimens of the lung cancer are needed.