PKR, a p53 target gene, plays a crucial role in the tumor-suppressor ...
Clinical significance of p53 tumor suppressor gene abnormalities in lung cancer
1
38 134 135 PATHOLOGICAL ANALYSIS OF JAPANESE LUNG CANOER IN THE AGED T.SATO, Y.ITO, O.MIYAISHI,H.TAUCHI AND T. YAMAMOTO* Institute for Medical Science of Aging, Aichi Medical University, Aichi, and *Nagoya Koseiin Geriatric Hospital, Nagoya, JAPAN Autopsy cases of primary cancer of the lung of 47 males aged 61-90 years and 39 females aged 57-99 years in the last 20 years have been oatholoaically analyzed. Lunq cancer cases were more frequently seen in the age between 75-04 in the male and 57-84 in th.e female. Organ and/or lymph node metastasis was observed in all cases of small cell carcinoma and also of the lung cancer directly related to the cause of death. In the male case, lymph node meta- stasis was more frequently noticed in case of epidermoid carcinoma than adenocarcinoma. Above 85 years of age, both in males and females, organ and/or lymph node metastasis became less frequent. And also case of lung cancer directly related to the cause of death decreased in number with increasing age. No lung cancer was observed in the 56 centenarians from the autopsy records during recent 30 years in all over Japan. 136 DETECTION OF SLX IN CARCINOMA OF THE LUNG T. Kinoshita., K. Wada, S. Namikawa, M. Kusagawa Anjo Kosei Hospital*, Mie Univers.Schoolof Medicine, Anjo-city Japan We have utilized FH6, a specific monoclonal antibody to SLX. to investigate the distribution of SLX in lung cancers. Our preliminary study revealedthat SLX was detectedmore specifically in adc (798, n=l4) than squamouscell carcinoma (712, n=15) or small cell carcinoma (05, n=5). Surgicalspecimens from 14 patients with adc of the lung were used for CEA and CA19-9 to comparewith the intensity of the positive staining of FH6. All cases of well diff. adc (n=5) and moderately diff. adc (n.6)demonstrated positive staining of FH6. However, poorlydiff. adc (n.3) provedFH6-negative. In elevenFH6-positive cases, CEA was detectedonly in 64% and CA19-9 in 56%. The serum SLX, CEA and CA19-9levelswere also measuredby radioimmunoassay in the same patients. High levelsof SLX were observedin only 6 cases of well and moderately diff. adc (55%);CEA in 7 cases (64%); and CA19-9 in 1 cases (9%). The levelsof three antigens were not elevatedin the serum of poorlydiff. ado cases. These resultssuggestthat althoughSLX sometimes fails to appearin the serum,it is a more specificantigento well and moderately diff. adc of the lung than CEA or CA19-9. Clinical significance of p53 tumor suppressor gene abnormalities in lung cancer H. Hiyoshi, Y. Matsuno, M. Noguchi, H. Kato, Y. Shimosato, S. Hirohashi. National Cancer Center and Tokyo Medical College, Tokyo A good correlation between p53 gene mutation and immunohistochemical p53 nuclear localization has been shown. Using acetone- fixed, paraffin-embedded sections, we analyzed the relationship between p53 nuclear localization and extent of disease on 88 lung cancer by histological type. About one half of the cases showed positive nuclear staining of tumors, but no corres- ponding normal lung tissue did. Fifteen of 26 squamous cell carcinoma (57%) disclosed positive staining. However, no relationship was observed between p53 staining and age, sex, smoking history, TNM factors and degree of histologic differentiation. In adenocarcinoma, 20 of 46 (43%) showed positive nuclear staining, and it correlated significantly with regional lymph node and distant organ metastases and advance in pathological stage, indicating p53 nuclear staining to be a good parameter associated with higher malignancy of tumors. Another clinically significant aspect of p53 mutation is usefulness of the site of point mutation in determining whether tumors are metastatic or multicentric in origin. An example will be presented. 137 FAMILIAL NON SMALL CELL BRONCHOGENIC CARCINOMA (NSCLC):A CLINIC-PATHOLOGICAL STUDY OF FOUR SIBLINGS. H. Biran and J. Goldstein. Soroka Medical Center, Beer- Sheba and Sheibe Institute of Oncology, Rehovot, Israel. Over a span of 6 years, four brothers, smokers, ages 43-54, presented with cancer of the right lung, RUL in 314. They shared a clinical pattern characterized by prominent mediastinal involvement, resistance to cisplatin-based chemotherapy and a relentless progression, leading to their demise within 14 months from diagnosis All tumours were poorly differentiated. By haematoxylin/eosin (HE) staining each subtype (squamous-, adeno- and large cell) was presented once. One case,with upfront cerebral presentation, might have been, by H&E morphology, a SCLC. However, avidin- biotin peroxidase immunostaining was uniformly negative for neuron-specific enolase, while positive for cytokeratin and epithelial membrane antigens. We presume that a) a genetic predisposition to exogenous carcinogens and b) a rare autosomal gene (JNCI 1990; 82:1272-9), could account for this unusual familial NSCLC clustering. One patient-derived cell line is available for further studies.
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Transcript of Clinical significance of p53 tumor suppressor gene abnormalities in lung cancer
38
134 135
PATHOLOGICAL ANALYSIS OF JAPANESE LUNG CANOER IN THE AGED
T.SATO, Y.ITO, O.MIYAISHI,H.TAUCHI AND T. YAMAMOTO* Institute for Medical Science of Aging, Aichi Medical University, Aichi, and *Nagoya Koseiin Geriatric Hospital, Nagoya, JAPAN
Autopsy cases of primary cancer of the lung of 47 males aged 61-90 years and 39 females aged 57-99 years in the last 20 years have been oatholoaically analyzed.
Lunq cancer cases were more frequently seen in the age between 75-04 in the male and 57-84 in th.e female. Organ and/or lymph node metastasis was observed in all cases of small cell carcinoma and also of the lung cancer directly related to the cause of death. In the male case, lymph node meta- stasis was more frequently noticed in case of epidermoid carcinoma than adenocarcinoma.
Above 85 years of age, both in males and females, organ and/or lymph node metastasis became less frequent. And also case of lung cancer directly related to the cause of death decreased in number with increasing age.
No lung cancer was observed in the 56 centenarians from the autopsy records during recent 30 years in all over Japan.
136
DETECTION OF SLX IN CARCINOMA OF THE LUNG
T. Kinoshita., K. Wada, S. Namikawa, M. Kusagawa Anjo Kosei Hospital*, Mie Univers. School of Medicine, Anjo-city Japan
We have utilized FH6, a specific monoclonal antibody to SLX. to investigate the distribution of SLX in lung cancers. Our preliminary study revealed that SLX was detected more specifically in adc (798, n=l4) than squamous cell carcinoma (712, n=15) or small cell carcinoma (05, n=5). Surgical specimens from 14 patients with adc of the lung were used for CEA and CA19-9 to compare with the intensity of the positive staining of FH6. All cases of well diff. adc (n=5) and moderately diff. adc (n.6) demonstrated positive staining of FH6. However, poorly diff. adc (n.3) proved FH6-negative. In eleven FH6-positive cases, CEA was detected only in 64% and CA19-9 in 56%. The serum SLX, CEA and CA19-9 levels were also measured by radioimmunoassay in the same patients. High levels of SLX were observed in only 6 cases of well and moderately diff. adc (55%); CEA in 7 cases (64%); and CA19-9 in 1 cases (9%). The levels of three antigens were not elevated in the serum of poorly diff. ado cases. These results suggest that although SLX sometimes fails to appear in the serum, it is a more specific antigen to well and moderately diff. adc of the lung than CEA or CA19-9.
Clinical significance of p53 tumor suppressor gene abnormalities in lung cancer
H. Hiyoshi, Y. Matsuno, M. Noguchi, H. Kato, Y. Shimosato, S. Hirohashi. National Cancer Center and Tokyo Medical College, Tokyo
A good correlation between p53 gene mutation and immunohistochemical p53 nuclear localization has been shown. Using acetone- fixed, paraffin-embedded sections, we analyzed the relationship between p53 nuclear localization and extent of disease on 88 lung cancer by histological type.
About one half of the cases showed positive nuclear staining of tumors, but no corres- ponding normal lung tissue did. Fifteen of 26 squamous cell carcinoma (57%) disclosed positive staining. However, no relationship was observed between p53 staining and age, sex, smoking history, TNM factors and degree of histologic differentiation.
In adenocarcinoma, 20 of 46 (43%) showed positive nuclear staining, and it correlated significantly with regional lymph node and distant organ metastases and advance in pathological stage, indicating p53 nuclear staining to be a good parameter associated with higher malignancy of tumors.
Another clinically significant aspect of p53 mutation is usefulness of the site of point mutation in determining whether tumors are metastatic or multicentric in origin. An example will be presented.
137
FAMILIAL NON SMALL CELL BRONCHOGENIC CARCINOMA (NSCLC):A CLINIC-PATHOLOGICAL STUDY OF FOUR SIBLINGS. H. Biran and
J. Goldstein. Soroka Medical Center, Beer- Sheba and Sheibe Institute of Oncology, Rehovot, Israel. Over a span of 6 years, four brothers, smokers, ages 43-54, presented with cancer of the right lung, RUL in 314. They shared a clinical pattern characterized by prominent mediastinal involvement, resistance to cisplatin-based chemotherapy and a relentless progression, leading to their demise within 14 months from diagnosis All tumours were poorly differentiated. By haematoxylin/eosin (HE) staining each subtype (squamous-, adeno- and large cell) was presented once. One case,with upfront cerebral presentation, might have been, by H&E morphology, a SCLC. However, avidin- biotin peroxidase immunostaining was uniformly negative for neuron-specific enolase, while positive for cytokeratin and epithelial membrane antigens. We presume that a) a genetic predisposition to exogenous carcinogens and b) a rare autosomal gene (JNCI 1990; 82:1272-9), could account for this unusual familial NSCLC clustering. One patient-derived cell line is available for further studies.
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