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680 The clinicopathological significance of p53 and Rb protein expressions in primary lung cancer. An experience of 220 cases
174
I677
Biology
Differentiation of atypical adenomatous hyperplasia and adenocarcinoma of the lung using DNA ploidy analysis and morphometry
Michiya Yokozaki ‘, Tetsuro Kodama2, Tomoyuki Yokose 3, Takeo Matsumoto4, Kiyoshi Mukai 3. ‘2nd Dept. lnern Med, Hiroshima Unir, Horoshima; 2Div. Thoracic Oncology National Cancer Center Hospital East, Chiba; 3Patho/ogy Div., National Cancer Center Research institute East; 4C/inica/ Laboratory Dk, National Cancer Center Hospital East, Chiba, Japan Atypical adenomatous hyperplasia (AAH) of the lung has been regarded as a precancerous lesion of lung adenocarcinoma, but the biological significance of this lesion is still not well understood. In this study, DNA histogram patterns and nuclear size were examined using an image cytometer. Fourteen cases of type II pneumocyte hyperplasia (HP), 7 cases of adenomatous hyperplasia with slight or no nuclear atypia (AH), 21 cases of AAH and 26 cases of adenocarcinoma were studied. The difference in mean nuclear sizes between HP (32.08 Frn”) and AH (32.86 pm2) was not significant, but between AH, AAH (38.52 pm*) and well differentiated (W/D) adenocarcinomas with mild nuclear atypia (51.12 pm2) statistically significant differences were observed (P < 0.05). Seven of 21 cases (33%) of AAH and 22 of 26 cases (85%) of adenocarcinoma showed aneuploid histogram patterns. The difference in the incidence of aneuploid pattern between AAH and adenocarcinoma was statistically significant (P < 0.01). All cases of HP and AH were diploid. Two of seven aneuploid AAH showed hyperdiploid DNA histogram patterns, and the remaining five showed polyploid histogram patterns with diploid and hyperdiploid stem lines. In these five cases, the small-size nuclei showed a diploid stem line and the largesize nuclei showed a hyperdiploid stem line. Our data indicated that AAH can be distinguished from HP, AH or adenocarcinoma by morphometry, and that some AAH that display aneuploid histogram patterns are precancerous lesions that may lead to adenocarcinoma.
I
678
I679
Anti calretinin anti serum: A new tool in the cytological evaluation of serous eff usions
M.C.P. Barberis’, U. Borghini’, S. Veronese3, M. Faleri3, C. Casadio4, G. Viale4. ‘Medical Foundation “E. BernardeW, Paderno D; 4Dept of Pathology, University of Milan, Eur. Inst. of Oncology; 3 Dept of Patholog)! Niguarda Hospital, Milan; 2Dept. of Pneumology, Niguarda Hospital, Milan, ltaly Commercially available antibodies suitable for positive identification of mesothelial cells are scarce and often, with reduced sensitivity and specificity. Objective of the present study was to document that a polyclonal antiserum to calretinin, a 29 kD calcium binding protein, consistently decorates normal and tumor mesothelial cells in cytological preparations. 33 archival cytological specimens from 8 patients with histologically confirmed malignant mesothelioma and 13 with metastatic serous effusion were de-stained and then immunostained with anti calretinin antiserum. For investigation on cell suspensions, 4 pleural fluids were incubated with anticalretinin antiserum. After cytocentrifugation the specimens were stained according the APAAP method. For electron microscopical examination the cell suspensions were then incubated with a gold-labelled anti-rabbit antibody. The diagnostic sensitivity of this new immunocytochemical approach reached 100% for the 8 malignant mesotheliomas investigated. Only 3 of the 13 adenocarcinomas metastatic to the serous membranes included in this study were weakly reactive, accounting for 81% specificity. Binding of anti- calretinin antiserum to living mesothelial cells was consistently documented in all the 4 cases investigated. It is concluded that calretinin is a most useful marker for positive identification of normal and tumor mesothelial cells in serous effusions. The capability of mesothelial cells to bind anti-calretinin in vivo might offer a basic rationale for developing new immunotherapeutic strategies for malignant mesotheliomas.
Study on long-term follow-up of atypical adenomatous hyperplasia (AAH) of the lung
T. Kodama, M. Yokozaki ‘, K. Nagai, Y. Nishiwaki, K. Takahashi, M. Nishimura, J. Yoshida, F. Hojo. National Cancer Center Hospital Kashiwa; ’ Hiroshima Unk!, Hiroshima, Japan
East,
We performed a follow-up study of lung cancer patients with AAH in the resected lung to clarify whether AAH represents precancerous lesions of lung adenocarcinoma (Ad). Three hundred nineteen surgically resected lung cancer cases from 1985 to 1989, without prior therapy, were followed up to evaluate the adenomatous lesions and their clinical features. We found 80 cases (25%) of adenomatous lesions, consisting of 38 cases (12%) of AAH and 60 cases (19%) of adenomatous hyperplasia with slight or no nuclear atypia (AH). In Ad, the incidence of AAH (22/159, 15%) was clearly higher than with squamous cell carcinoma (Sq) (5/121, 4%), with a significant difference (p < 0.01). AAH occurred frequently in simultaneous double cancer (8/15, 53%) with a significant difference (p < 0.01). The median follow-up time (MFT) of the 319 patients was six and a half years; 160 patients died (MFT, 20 mos; follow-up duration, O-124 mos) and 159 patients have survived (MFT, 79 mos; duration, 33-137 mos). There were four cases of metachronous double primary cancers (three cases with Sq followed by Sq, and one case with Ad followed by Ad). We found no evidence that the development of the second Ad grew out of AAH in the metachronous Ad case, because there was no AAH in the resected lung. In contrast, we found abnormal tumorous shadows in two cases with AAH in the resected lung. We could not confirm whether these lesions were histologically malignant. These results indicate a close relationship between AAH and Ad. The clinical significance of AAH may be clarified by a longer follow up.
Tuesday, 12 August 1997 POSTER
SESSION
Pathology I 680
The clinicopathological significance of p53 and Rb protein expressions in primary lung cancer. An experience of 220 cases
Y.C. Lee, Y.L. Chang, Taiwan
S.P. Luh, C.M. Lee. Nat/. Taiwan Univ. Hosp.,
Taipei,
The expression of ~53 and Rb genes have been implicated in neoplasm and they are involved in cell growth and apoptosis in several types of epithelial malignancies. However, no final conclusion of the relationship between ~53 or Rb expression and clinical parameters in lung cancer is made. Formal in-fixed paraffin-embedded tissue sections from 220 cases [102 adenocarcinomas (AC), 75 squamous cell carcinomas (SCC), 36 bronchioloalveolar carcinomas (BAC) and 7 small cell carcinomas (SmCC)] of lung cancer were studied immunohistochemically based on the percentage of ~53 and Rb expressions of tumor cells. The expression was then compared with indicators of prognosis and biological behavior of the tumors. P53 was detectable in 123 of the 220 cases (56%), including 39/75 (52%) SCCs, 58/102 (57%) ACs, 20/36 (55.5%) BACs and 6/7 (86%) SmCCs. The ~53 expression was higher in patients with lymph node metastasis (p = 0.0397) and poor clinical survival (p:O.OOO). In addition, an inverse relationship was also found between the anti-oncogene protein product ~53 and Rb (p = 0.000). These results suggest that ~53 accumulation and altered Rb protein expression in lung cancer may have prognostic importance.
I677
Biology
Differentiation of atypical adenomatous hyperplasia and adenocarcinoma of the lung using DNA ploidy analysis and morphometry
Michiya Yokozaki ‘, Tetsuro Kodama2, Tomoyuki Yokose 3, Takeo Matsumoto4, Kiyoshi Mukai 3. ‘2nd Dept. lnern Med, Hiroshima Unir, Horoshima; 2Div. Thoracic Oncology National Cancer Center Hospital East, Chiba; 3Patho/ogy Div., National Cancer Center Research institute East; 4C/inica/ Laboratory Dk, National Cancer Center Hospital East, Chiba, Japan Atypical adenomatous hyperplasia (AAH) of the lung has been regarded as a precancerous lesion of lung adenocarcinoma, but the biological significance of this lesion is still not well understood. In this study, DNA histogram patterns and nuclear size were examined using an image cytometer. Fourteen cases of type II pneumocyte hyperplasia (HP), 7 cases of adenomatous hyperplasia with slight or no nuclear atypia (AH), 21 cases of AAH and 26 cases of adenocarcinoma were studied. The difference in mean nuclear sizes between HP (32.08 Frn”) and AH (32.86 pm2) was not significant, but between AH, AAH (38.52 pm*) and well differentiated (W/D) adenocarcinomas with mild nuclear atypia (51.12 pm2) statistically significant differences were observed (P < 0.05). Seven of 21 cases (33%) of AAH and 22 of 26 cases (85%) of adenocarcinoma showed aneuploid histogram patterns. The difference in the incidence of aneuploid pattern between AAH and adenocarcinoma was statistically significant (P < 0.01). All cases of HP and AH were diploid. Two of seven aneuploid AAH showed hyperdiploid DNA histogram patterns, and the remaining five showed polyploid histogram patterns with diploid and hyperdiploid stem lines. In these five cases, the small-size nuclei showed a diploid stem line and the largesize nuclei showed a hyperdiploid stem line. Our data indicated that AAH can be distinguished from HP, AH or adenocarcinoma by morphometry, and that some AAH that display aneuploid histogram patterns are precancerous lesions that may lead to adenocarcinoma.
I
678
I679
Anti calretinin anti serum: A new tool in the cytological evaluation of serous eff usions
M.C.P. Barberis’, U. Borghini’, S. Veronese3, M. Faleri3, C. Casadio4, G. Viale4. ‘Medical Foundation “E. BernardeW, Paderno D; 4Dept of Pathology, University of Milan, Eur. Inst. of Oncology; 3 Dept of Patholog)! Niguarda Hospital, Milan; 2Dept. of Pneumology, Niguarda Hospital, Milan, ltaly Commercially available antibodies suitable for positive identification of mesothelial cells are scarce and often, with reduced sensitivity and specificity. Objective of the present study was to document that a polyclonal antiserum to calretinin, a 29 kD calcium binding protein, consistently decorates normal and tumor mesothelial cells in cytological preparations. 33 archival cytological specimens from 8 patients with histologically confirmed malignant mesothelioma and 13 with metastatic serous effusion were de-stained and then immunostained with anti calretinin antiserum. For investigation on cell suspensions, 4 pleural fluids were incubated with anticalretinin antiserum. After cytocentrifugation the specimens were stained according the APAAP method. For electron microscopical examination the cell suspensions were then incubated with a gold-labelled anti-rabbit antibody. The diagnostic sensitivity of this new immunocytochemical approach reached 100% for the 8 malignant mesotheliomas investigated. Only 3 of the 13 adenocarcinomas metastatic to the serous membranes included in this study were weakly reactive, accounting for 81% specificity. Binding of anti- calretinin antiserum to living mesothelial cells was consistently documented in all the 4 cases investigated. It is concluded that calretinin is a most useful marker for positive identification of normal and tumor mesothelial cells in serous effusions. The capability of mesothelial cells to bind anti-calretinin in vivo might offer a basic rationale for developing new immunotherapeutic strategies for malignant mesotheliomas.
Study on long-term follow-up of atypical adenomatous hyperplasia (AAH) of the lung
T. Kodama, M. Yokozaki ‘, K. Nagai, Y. Nishiwaki, K. Takahashi, M. Nishimura, J. Yoshida, F. Hojo. National Cancer Center Hospital Kashiwa; ’ Hiroshima Unk!, Hiroshima, Japan
East,
We performed a follow-up study of lung cancer patients with AAH in the resected lung to clarify whether AAH represents precancerous lesions of lung adenocarcinoma (Ad). Three hundred nineteen surgically resected lung cancer cases from 1985 to 1989, without prior therapy, were followed up to evaluate the adenomatous lesions and their clinical features. We found 80 cases (25%) of adenomatous lesions, consisting of 38 cases (12%) of AAH and 60 cases (19%) of adenomatous hyperplasia with slight or no nuclear atypia (AH). In Ad, the incidence of AAH (22/159, 15%) was clearly higher than with squamous cell carcinoma (Sq) (5/121, 4%), with a significant difference (p < 0.01). AAH occurred frequently in simultaneous double cancer (8/15, 53%) with a significant difference (p < 0.01). The median follow-up time (MFT) of the 319 patients was six and a half years; 160 patients died (MFT, 20 mos; follow-up duration, O-124 mos) and 159 patients have survived (MFT, 79 mos; duration, 33-137 mos). There were four cases of metachronous double primary cancers (three cases with Sq followed by Sq, and one case with Ad followed by Ad). We found no evidence that the development of the second Ad grew out of AAH in the metachronous Ad case, because there was no AAH in the resected lung. In contrast, we found abnormal tumorous shadows in two cases with AAH in the resected lung. We could not confirm whether these lesions were histologically malignant. These results indicate a close relationship between AAH and Ad. The clinical significance of AAH may be clarified by a longer follow up.
Tuesday, 12 August 1997 POSTER
SESSION
Pathology I 680
The clinicopathological significance of p53 and Rb protein expressions in primary lung cancer. An experience of 220 cases
Y.C. Lee, Y.L. Chang, Taiwan
S.P. Luh, C.M. Lee. Nat/. Taiwan Univ. Hosp.,
Taipei,
The expression of ~53 and Rb genes have been implicated in neoplasm and they are involved in cell growth and apoptosis in several types of epithelial malignancies. However, no final conclusion of the relationship between ~53 or Rb expression and clinical parameters in lung cancer is made. Formal in-fixed paraffin-embedded tissue sections from 220 cases [102 adenocarcinomas (AC), 75 squamous cell carcinomas (SCC), 36 bronchioloalveolar carcinomas (BAC) and 7 small cell carcinomas (SmCC)] of lung cancer were studied immunohistochemically based on the percentage of ~53 and Rb expressions of tumor cells. The expression was then compared with indicators of prognosis and biological behavior of the tumors. P53 was detectable in 123 of the 220 cases (56%), including 39/75 (52%) SCCs, 58/102 (57%) ACs, 20/36 (55.5%) BACs and 6/7 (86%) SmCCs. The ~53 expression was higher in patients with lymph node metastasis (p = 0.0397) and poor clinical survival (p:O.OOO). In addition, an inverse relationship was also found between the anti-oncogene protein product ~53 and Rb (p = 0.000). These results suggest that ~53 accumulation and altered Rb protein expression in lung cancer may have prognostic importance.