pro-gastrin-releasing peptide is a monitoring tumor marker for evaluation of chemotherapy effects in...

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38 142 143 A CLINICOPATHOLOGICAL STUDY ON FEMALE SQUAMOUS CELL CARCINOMA OF LUNG. M. Aoe. M. Nakata, N. Shimizu, K. Okabe, S. Mortyama, A. Ando. The second Department of Surgery, Okayama University Medical School, Okayama. Japan. It is well known that cigarette smoking is one of the major risk factor of squamous cell lung carcinoma (SCLC). In Japan, female smoker is still rarer than male. Thus, there may be a sexual difference in clinicopathological feature of SCLC. In this study, we analyzed female SCLC cases fmm clinical and pathological points of view. Additionally, an immunohistochemical study was performed using two types of antisera such as anti-keratin squamous epithelium antibody ( kemSE ) and anti-keratin nonsquamous eptthelium antibody ( keraNSE). From January 1976 through August 1992, there were 1106 cases of lung carcinoma in our institute and 436 cases of them were diagnosed as SCLC pathologically (39.4%). Thirty five cases out of 436 were female and the female-to-male ratio of SCLC was I:1 1.5. There were 19 non-smokers among the female cases (54.3%). however most male patients had a smoking history. The tumor site also showed a remarkable contrast between males and females, with 71.4% of 35 female cases being peripheral type, compared with 36.9% of male cases. There were no significant differences in the mean age, operability. and clinical stage. In ftfleen female cases, we could obtain adequate tumor specimen for the immunohistochemical study. keraSE + keraNSE + Female SCLC 9/i 5 (60.0%) 11115 (73.3%) poorly diff. 113 2l3 moderately diff. 4n 4n well diff. 415 z5 Male SCLC (selected at random) 1O/l 5 (66.7%) 5115 (33.3%) In female cases, eleven (73.3%) were positive for keraNSE, but only five (33.3%) were positive for keraNSE in fifteen male SCLC cases selected at random. This results suggested that female SCLC might have a different oncologic character from male SCLC. 144 HISTOPATHOLOGICAL STUDY OF ADENOCARCINOMA AND HYPERPLASTIC EPITHELIAL LESIONS IN THE PERIPHERAL LUNG . T. Kodama, K. Nagai, Y. Nishiwaki, K. Takahashi, M. Nishimura, J. Yoshida, F. Hojo, National Cancer Center Hospital East, Kashiwa, Japan. To clarify the relationship between adenocarcinoma and atypical adenomatous hyperplasia (AAH) which was considered to be a precancerous lesion of adenocarcinoma of the lung, multiple specimens, including lung tumors and non-neoplastic lung tissues, were examined histologically and immunohistochemically in 323 lung cancer cases surgically resected without any preoperative treatment. AAH occurred in 12% of cases and occurred more often in adenocarcinoma cases (17%) than in squamous cell carcinoma cases (5%). In multiple primary lung cancer cases, AAH occurred more frequently (67%) and multiply than in solitary lung cancer cases. There were 17% of adenocarcinoma cases, especially in well differentiated papillary adenocarcinoma cases, in the periphery of which AAH coexisted in the same tumor. In cases of multiple primary lung cancer cases, minute adenocarcinomas were centrally located in AAH. lmmunohistochemically, surfactant apoprotein-positive cells were present focally or diffusely in cases of adenocarcinomaand AAH. Therefore, it is suggested that some adenocarcinomas, especially well differentiated papillary adenocarcinoma might originate from AAH. Prognostic Significance of AgNORs and Nuclear Area in Resected Lung Adenocarcinoma. M. Shiba, Y. Yamaguchi, T. Iizasa, M. Baba, Y. Nomoto, H. Kono, E. Odaka, M. Otsuji, N. Tamiya, N. Iwai, T. Fujisawa Dept. of Surgery, Inst. of Pulmonary Cancer Res Chiba University, Chiba, Japan. To evaluate correlation to post surgical prognosis, tumor cell AgNORs ( argyrophil nucleolar organizer regions ) and nuclear area were estimated in surgically resected lung cancer patients with tumor stamp cytology specimens. Eighty-nine cases of resected lung cancer ( 52 adenocarcinomas, 34 squamous cell carcinomas and 3 other lung cancers ) were analyzed cytologically. AgNORs were stained by one step method after Ploton et al. and number was counted in 100 tumor cells. At the same time, nuclear area was measured by computer assisted morphometric system under microscopy ( Nikon Cosmozone). These findings were compared to tumor histopathological findings , pathological stage and surgical outcomes. Nuclear atypia and histolological differentiation of tumor correlated well with mean numbers of AgNORs per cell or mean nuclear area in adenocarcinoma ( p<O.OS ), but not in squamous cell carcinoma. Mean numbers of AgNORs showed linear correlation with mean nuclear area in both histology type ( pcO.05 ). When the cases were scored and divided into three groups according to mean numbers of AgNORs and nuclear area, low score group had higher survival rate than high score group, and survival curve showed statistically significant difference between them only in adenocarcinoma cases ( p<o.os ) 145 PRO-GASTRIN-RELEASING PEPTIDE IS A MONITORING TUMOR MARKER FOR EVALUATION OF CHEMOTHERAPY EFFECTS IN PATIENTS WITH SMALL CELL LUNG CANCER (SCLC). T. Kodama, Y. Nishiwaki, F. Hojo, K. Kubota, H. Ohmatsu, T. Matsumoto, R. Kakinuma, I. Sekine, M. Yokosaki, K. Yamaguchi, Y. Miyake, K. Aoyagi. National Cancer Center Hospital East, Chiba, National Cancer Center Research Institute, Tokyo, Tonen Co. Ltd., Saitama, Japan. Gastrin-releasing peptide (GRP) is a specific product of small cell lung carcinoma (SCLC) cells and serum GRP levels are specifically elevated in SCLC patients, Using the newly developed enzyme immunoassay for a carboxyl-terminal fragments of proGRP, proGRP (31-98), the clinical significance of serial measurement, especially in the correlation between the chemotherapy effects and serum proGRP levels, and the earlier detection of disease recurrence were evaluated in 23 SCLC patients. There were 9 cases in which serum proGRP was examined weekly up to 11 weeks after the onset of treatment. Serum proGRP levels before treatment were between 5,224 and 113.1 pg/ml (normal range: c47pglml). Good correlation between clinical response and serum proGRP levels was observed. In 14 cases which were followed up from 6 months to 36 months, there were 6 cases without recurrence and 8 cases with recurrence. In theformergroup, no exess level of serum proGRP was observed. In 5 cases of the latter, elevation of serum proGRP levels were already observed in 7, 6, 5, 5, and 1 months before the appearance of clinical recurrence. The remaning 3 cases showed no elevation of serum proGRP levels at the time of recurrence. These observations suggest that the serial determination of serum proGRP levels may represent a significant advance forthe treatment of SCLC patients.

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Page 1: Pro-gastrin-releasing peptide is a monitoring tumor marker for evaluation of chemotherapy effects in patients with small cell lung cancer (SCLC)

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142 143

A CLINICOPATHOLOGICAL STUDY ON FEMALE SQUAMOUS CELL CARCINOMA OF LUNG. M. Aoe. M. Nakata, N. Shimizu, K. Okabe, S. Mortyama, A. Ando. The second Department of Surgery, Okayama University Medical School, Okayama. Japan.

It is well known that cigarette smoking is one of the major risk factor of squamous cell lung carcinoma (SCLC). In Japan, female smoker is still rarer than male. Thus, there may be a sexual difference in clinicopathological feature of SCLC. In this study, we analyzed female SCLC cases fmm clinical and pathological points of view. Additionally, an immunohistochemical study was performed using two types of antisera such as anti-keratin squamous epithelium antibody ( kemSE ) and anti-keratin nonsquamous eptthelium antibody ( keraNSE).

From January 1976 through August 1992, there were 1106 cases of lung carcinoma in our institute and 436 cases of them were diagnosed as SCLC pathologically (39.4%). Thirty five cases out of 436 were female and the female-to-male ratio of SCLC was I:1 1.5. There were 19 non-smokers among the female cases (54.3%). however most male patients had a smoking history. The tumor site also showed a remarkable contrast between males and females, with 71.4% of 35 female cases being peripheral type, compared with 36.9% of male cases. There were no significant differences in the mean age, operability. and clinical stage.

In ftfleen female cases, we could obtain adequate tumor specimen for the immunohistochemical study.

keraSE + keraNSE + Female SCLC 9/i 5 (60.0%) 11115 (73.3%)

poorly diff. 113 2l3 moderately diff. 4n 4n well diff. 415 z5

Male SCLC (selected at random) 1 O/l 5 (66.7%) 5115 (33.3%) In female cases, eleven (73.3%) were positive for keraNSE, but only five

(33.3%) were positive for keraNSE in fifteen male SCLC cases selected at random.

This results suggested that female SCLC might have a different oncologic character from male SCLC.

144

HISTOPATHOLOGICAL STUDY OF ADENOCARCINOMA AND HYPERPLASTIC EPITHELIAL LESIONS IN THE PERIPHERAL LUNG . T. Kodama, K. Nagai, Y. Nishiwaki, K. Takahashi, M. Nishimura, J. Yoshida, F. Hojo, National Cancer Center Hospital East, Kashiwa, Japan.

To clarify the relationship between adenocarcinoma and atypical adenomatous hyperplasia (AAH) which was considered to be a precancerous lesion of adenocarcinoma of the lung, multiple specimens, including lung tumors and non-neoplastic lung tissues, were examined histologically and immunohistochemically in 323 lung cancer cases surgically resected without any preoperative treatment. AAH occurred in 12% of cases and occurred more often in adenocarcinoma cases (17%) than in squamous cell carcinoma cases (5%). In multiple primary lung cancer cases, AAH occurred more frequently (67%) and multiply than in solitary lung cancer cases. There were 17% of adenocarcinoma cases, especially in well differentiated papillary adenocarcinoma cases, in the periphery of which AAH coexisted in the same tumor. In cases of multiple primary lung cancer cases, minute adenocarcinomas were centrally located in AAH. lmmunohistochemically, surfactant apoprotein-positive cells were present focally or diffusely in cases of adenocarcinomaand AAH.

Therefore, it is suggested that some adenocarcinomas, especially well differentiated papillary adenocarcinoma might originate from AAH.

Prognostic Significance of AgNORs and Nuclear Area in Resected Lung Adenocarcinoma. M. Shiba, Y. Yamaguchi, T. Iizasa, M. Baba, Y. Nomoto, H. Kono, E. Odaka, M. Otsuji, N. Tamiya, N. Iwai, T. Fujisawa Dept. of Surgery, Inst. of Pulmonary Cancer Res Chiba University, Chiba, Japan.

To evaluate correlation to post surgical prognosis, tumor cell AgNORs ( argyrophil nucleolar organizer regions ) and nuclear area were estimated in surgically resected lung cancer patients with tumor stamp cytology specimens.

Eighty-nine cases of resected lung cancer ( 52 adenocarcinomas, 34 squamous cell carcinomas and 3 other lung cancers ) were analyzed cytologically. AgNORs were stained by one step method after Ploton et al. and number was counted in 100 tumor cells. At the same time, nuclear area was measured by computer assisted morphometric system under microscopy ( Nikon Cosmozone). These findings were compared to tumor histopathological findings , pathological stage and surgical outcomes.

Nuclear atypia and histolological differentiation of tumor correlated well with mean numbers of AgNORs per cell or mean nuclear area in adenocarcinoma ( p<O.OS ), but not in squamous cell carcinoma. Mean numbers of AgNORs showed linear correlation with mean nuclear area in both histology type ( pcO.05 ). When the cases were scored and divided into three groups according to mean numbers of AgNORs and nuclear area, low score group had higher survival rate than high score group, and survival curve showed statistically significant difference between them only in adenocarcinoma cases ( p<o.os )

145

PRO-GASTRIN-RELEASING PEPTIDE IS A MONITORING TUMOR MARKER FOR EVALUATION OF CHEMOTHERAPY EFFECTS IN PATIENTS WITH SMALL CELL LUNG CANCER (SCLC). T. Kodama, Y. Nishiwaki, F. Hojo, K. Kubota, H. Ohmatsu, T. Matsumoto, R. Kakinuma, I. Sekine, M. Yokosaki, K. Yamaguchi, Y. Miyake, K. Aoyagi. National Cancer Center Hospital East, Chiba, National Cancer Center Research Institute, Tokyo, Tonen Co. Ltd., Saitama, Japan.

Gastrin-releasing peptide (GRP) is a specific product of small cell lung carcinoma (SCLC) cells and serum GRP levels are specifically elevated in SCLC patients, Using the newly developed enzyme immunoassay for a carboxyl-terminal fragments of proGRP, proGRP (31-98), the clinical significance of serial measurement, especially in the correlation between the chemotherapy effects and serum proGRP levels, and the earlier detection of disease recurrence were evaluated in 23 SCLC patients.

There were 9 cases in which serum proGRP was examined weekly up to 11 weeks after the onset of treatment. Serum proGRP levels before treatment were between 5,224 and 113.1 pg/ml (normal range: c47pglml). Good correlation between clinical response and serum proGRP levels was observed. In 14 cases which were followed up from 6 months to 36 months, there were 6 cases without recurrence and 8 cases with recurrence. In theformergroup, no exess level of serum proGRP was observed. In 5 cases of the latter, elevation of serum proGRP levels were already observed in 7, 6, 5, 5, and 1 months before the appearance of clinical recurrence. The remaning 3 cases showed no elevation of serum proGRP levels at the time of recurrence. These observations suggest that the serial determination of serum proGRP levels may represent a significant advance forthe treatment of SCLC patients.