1
40 150 151 PROGNOSTIC VALllE OF THE NEW TUMOR MARKER CZFRA 21-1 IN NON-SMALL CELL LUNG CANCFX. J.Niklihski,M.Furman, E. Chyczewska, L.Chyczewski,F.Rogowski, J.LaudaAski Departments of: Thoracic Surgery, Pneumonology,Pathology and Nuclear Medicine, Medical School, Bialystok, Poland Cytokeratin 19 is particular-y abundant in lung carcinoma. 85 patients (pts) with non-small cell lung cancer- NSCLC (58bperable, 15 unresectabletumors, 12 proved distance metastasis) were investigatedto establish CYFRA 21-1 serum utility as a prognostic factor, using IRMA method (CIS bio GIF-SUR-YVETTE).CYFRA 21-1 assays were performed before surgery and serially after tumor resection. In the 73 pts qualified for thoracotomy,increased CYFRA 21-1 levels were observed in 52% (33% of stage I, 47% of stage II, 57% of stage IIIa, 67% of stage IIIb). In 12 pts with TNM IV CYFRA 21-1 elevated levels were obtained in 75% CYFRA 21-1 levels were significantlylower in 58 pts with resectable tumors than in 15 cases with unresectable (p< 0.02). The study proved that CYFRA 21-1 preoperative determinationand the course of levels of this marker during follow-up was important. Pretreatment elevation resulted in poorer patient survival. Complete resection resulted in a significantdrop in serum CYFRA 21-1 levels in 16 pts who had elevated marker level before surgery and no further disease evidence. In 14 of 58 who survived complete resection, recurrence were subsequentlydetected. The percentage of recurrence in patients with normal postoperativeCYFRA 21-1 levels was 2.3% (l/43). The percentageof recurrence in pts with CYFRA postoperative elevated levels was significantlyhigher and equaled 87% (13/15). In 11 of 13 pts with recurrence after complete resection, recurrent elevation of CYFRA 21-1 preceded changes detectable by CT or clinical examination by 2 to 6 months. In conclusion, CYFRA 21-1 appears to be a useful prognostic marker in NSCLC. 152 EVALUATION OF A NEW SERUM TUMOR MARKER CYFRA 21.1 FOR THE DIAGNOSIS AND PROGNOSIS OF NON SMALL CELL LUNG CANCER (NSCLL) : PRELIMINARY RESULTS. JM. Br&hot*, J.Nataf**, J.F&ult**, MF.D&*, B. Tbirion***, J.Miltgen*, J. Rochemaure* - * Service de F’neumologie, ** Labaatoire Biophysique, H&l- Dia. 75004 PARIS. **I* L.abomtoire Cis-Bio intemational. m : Analysis of swum CYFRA 21.1 concentrations before. and after treatment in NSCLC patients (pts), accordiig to histology, TNM, response to treatment and overall survival. Me&& : _ Prospective study with measure by immumradiometric assay of smun concentrations of CYFRA 21.1, carcincembryonic antigen (CEA), squamous cell carcinoma antigen @CC), CA 125, CA 19.9, neumn-specific an&se (NSE) in resectableand umesectable NSCLC. I&!&: w : 7 pts (6 M ,1 F) ; 2 squamous cell (SC) carcinoma, 5 adenowcinomn (ADC) ; 3 stage I, 2 stage II, 2 stage mA; Cylia 21-I > 3,6 ng/ml in 1 (with stage I SC carcinoma) before resection and normal after resection. GrwwII:22pts(13M,9F);llSC carcinoma, 7 ADC, 3 large cell carcinoma (LCC), 1 composite (SC + small cell carcinoma) ; 9 stage III B, 12 stage IV, 1 stage (I). Cyiin21.1 elevatedin 13 (mean 24.1, 4.0 to 89) : S/l1 SC carcinoma, 317 ADC, 2i3 LCC ; SCC elevated in 4 out of 22, always associated to ao atmormal value of Cyfm 21.1 ; reduction ofserum value of Cyfra 21.1 in the 3 Pa&l Responses, in 1 Stable Disease, in 1 Progression ; seccmdary elevation in 1 Stable Disease and 2 Pmpssion. Conclusion : Inthis preliminary study, - Cytia21.1 serumconcentmtionsarealmcwmal in9/13 SC c~~cmoma, 3/12ADC, 213 LCC. - Abnormal values of Cyiia 21.1 are more Erequently observed in advanced NSCLC (l/7 resectable pts. 1302 unresectable pts). - There is a dramatically decrease of Cyfra 21 .l ccmcentralions in the 3 responders and in the resectable patient. The study is on-going. ROLE OF ELASTOTIC FRAMEWORK ON THE TUMOR DEVELOPMENT OF PERIPHERAL LUNG ADENOCARCINOMA LESS THAN 4 CM IN DIAMETER. T. Eto, H. Suzula, A. Honda,and Y.Nagashima. Shizuoka General Hospital, Shizuoka, Japan. Two hundred six patients of peripheral lung adenocarcinoma (PLA) less than 4 cm in diameter were studied histologically, morphometrically, radiographically and clinicopathologically in special reference to the stromal elastosis. We classified PLA mto two types from the stromal elastotic framework (FFW). Type 1(24 patients) had the preserved EFW consisting of constantly thick stroma. Type 2 (182 patients) revealed the disrupted EFW especially in the center of tumor forming central fibrosis (CF) where many air spaces were collapsed or collagenized. At the periphery of type 2, extending stroma (Exst) was formed with thin walled elastic framework similar to normal alveoli (NA). From the image analysis, increased amounts of elastic fibers could be calculated in type 1 ( 3.3-9.7 fold) and type 2 ( 3.9-7.6 fold) EFW compared to NA, which mean the contraction rate of pre-existing NA. In contrast, Exst in type 2 contained 0.8-2.1 fold of the fibers compared to NA suggesting mild-reacting pre-existing NA. Radiographically, in type 1, tumor size hardly enlarged and the density tended to increase gradually over a long time. In type 2, tumor size tended to increase abruptly over a short time. As prognosis of patients who were followed more than 3 years, 50% had relapsed in type 2, but none in type 1. Conclusion ; Tumor stroma in the early stage of PLA might show the preserved EFW (type 1) formed by contractmg and thickening reaction of NA. As tumor developing, disrupted EFW (type 2) form CF with Exst. It indicate the stromal invasion and directly reflect to the prognosis. 153 CHRONIC INHALATION OF URBAN AMBIENT AIR INDU=s MUl_TlF‘ !CAL NEUROENWCRlNE CELL PAF’ ILLOMAS AND HYPERPLASIA IN THE RAT AIRWAY EF’ ITHELIUM. M. Kanisawa, T. Shibagaki, H. Kitamurrr. T- It% Y. lnayama. wept. Path&, Yokohama City Univ. Schwa1 of Medicine, Yokdaama, Japan. The real cause and pathogenesis of smal1 cell lung cancer are still uncertain due to lacking of the proper animal model. This paper reports chronic inhalation Of urban ambient air chiefly polluted with automobile exhaust gas induces a high incidence of neuroendocrine cell PapillOmaS and hyperplasia in the rat airway epithelium. Sixty-six male Wistar rats were exposed to pollutd air in the animal facilities installed on a street with heavy traffic in down- tow” Yokohama. Nontreated control rats were bred in the university aimal facilities is supplied Hepa-filtered air. Densities of NOX. SOz axl dust particles were recorded during the experment. Animals were sacrificed at the 26, 52 and 78 experimental weeks and the lungs were examined histogically by serial sections. Production of multiple papiliomas in the mid to small bronchi and foci of atypical cell hyperplasia mostly found in the bronchioli, particular- ly in the brcnchio~oalveoIar region were frequently observed in the rat exposed for 7X weeks. Certain “umber of the cells composing these neoplastic lesion showed positive reaction immtntohistochemically to calcitonine genera lated peptide (CGRP). Development of the usual type of adenocarcinoma wz found in 2 rats exposed for 78 weeks. Significant difference between the inhaled air in both groups was detected only in the contents of dust particles. These results may suggest urban ambient air densely polluted with dust particles derived from automobile exhaust gas may be a possible cause of pulmonary neurcendacrine cell tumor in human.

Role of elastotic framework on the tumor development of peripheral lung adenocarcinoma less than 4 cm in diameter

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Page 1: Role of elastotic framework on the tumor development of peripheral lung adenocarcinoma less than 4 cm in diameter

40

150 151

PROGNOSTIC VALllE OF THE NEW TUMOR MARKER CZFRA 21-1 IN NON-SMALL CELL LUNG CANCFX. J.Niklihski, M.Furman, E. Chyczewska, L.Chyczewski, F.Rogowski, J.LaudaAski Departments of: Thoracic Surgery, Pneumonology, Pathology and Nuclear Medicine, Medical School, Bialystok, Poland Cytokeratin 19 is particular-y abundant in lung carcinoma.

85 patients (pts) with non-small cell lung cancer- NSCLC (58bperable, 15 unresectable tumors, 12 proved distance metastasis) were investigated to establish CYFRA 21-1 serum utility as a prognostic factor, using IRMA method (CIS bio GIF-SUR-YVETTE). CYFRA 21-1 assays were performed before surgery and serially after tumor resection. In the 73 pts qualified for thoracotomy, increased CYFRA

21-1 levels were observed in 52% (33% of stage I, 47% of stage II, 57% of stage IIIa, 67% of stage IIIb). In 12 pts with TNM IV CYFRA 21-1 elevated levels were obtained in 75% CYFRA 21-1 levels were significantly lower in 58 pts with resectable tumors than in 15 cases with unresectable (p< 0.02). The study proved that CYFRA 21-1 preoperative determination and the course of levels of this marker during follow-up was important. Pretreatment elevation resulted in poorer patient survival. Complete resection resulted in a significant drop in serum CYFRA 21-1 levels in 16 pts who had elevated marker level before surgery and no further disease evidence. In 14 of 58 who survived complete resection, recurrence were subsequently detected. The percentage of recurrence in patients with normal postoperative CYFRA 21-1 levels was 2.3% (l/43). The percentage of recurrence in pts with CYFRA postoperative elevated levels was significantly higher and equaled 87% (13/15). In 11 of 13 pts with recurrence after complete resection, recurrent elevation of CYFRA 21-1 preceded changes detectable by CT or clinical examination by 2 to 6 months. In conclusion, CYFRA 21-1 appears to be a useful prognostic marker in NSCLC.

152

EVALUATION OF A NEW SERUM TUMOR MARKER CYFRA 21.1 FOR THE DIAGNOSIS AND PROGNOSIS OF NON SMALL CELL LUNG CANCER (NSCLL) : PRELIMINARY RESULTS. JM. Br&hot*, J.Nataf**, J.F&ult**, MF.D&*, B. Tbirion***, J.Miltgen*, J. Rochemaure* - * Service de F’neumologie, ** Labaatoire Biophysique, H&l- Dia. 75004 PARIS. **I* L.abomtoire Cis-Bio intemational.

m : Analysis of swum CYFRA 21.1 concentrations before. and after treatment in NSCLC patients (pts), accordiig to histology, TNM, response to treatment and overall survival.

Me&& : _ Prospective study with measure by immumradiometric assay of smun concentrations of CYFRA 21.1, carcincembryonic antigen (CEA), squamous cell carcinoma antigen @CC), CA 125, CA 19.9, neumn-specific an&se (NSE) in resectable and umesectable NSCLC.

I&!&: w : 7 pts (6 M ,1 F) ; 2 squamous cell (SC) carcinoma, 5 adenowcinomn (ADC) ; 3 stage I, 2 stage II, 2 stage mA; Cylia 21-I > 3,6 ng/ml in 1 (with stage I SC carcinoma) before resection and normal after resection. GrwwII:22pts(13M,9F);llSC carcinoma, 7 ADC, 3 large cell carcinoma (LCC), 1 composite (SC + small cell carcinoma) ; 9 stage III B, 12 stage IV, 1 stage (I). Cyiin21.1 elevatedin 13 (mean 24.1, 4.0 to 89) : S/l1 SC carcinoma, 317 ADC, 2i3 LCC ; SCC elevated in 4 out of 22, always associated to ao atmormal value of Cyfm 21.1 ; reduction of serum value of Cyfra 21.1 in the 3 Pa&l Responses, in 1 Stable Disease, in 1 Progression ; seccmdary elevation in 1 Stable Disease and 2 Pmpssion.

Conclusion : In this preliminary study, - Cytia21.1 serumconcentmtionsarealmcwmal in9/13 SC c~~cmoma, 3/12ADC, 213 LCC. - Abnormal values of Cyiia 21.1 are more Erequently observed in advanced NSCLC (l/7 resectable pts. 1302 unresectable pts). - There is a dramatically decrease of Cyfra 21 .l ccmcentralions in the 3 responders and in the resectable patient. The study is on-going.

ROLE OF ELASTOTIC FRAMEWORK ON THE TUMOR DEVELOPMENT OF PERIPHERAL LUNG ADENOCARCINOMA LESS THAN 4 CM IN DIAMETER. T. Eto, H. Suzula, A. Honda, and Y. Nagashima. Shizuoka General Hospital, Shizuoka, Japan.

Two hundred six patients of peripheral lung adenocarcinoma (PLA) less than 4 cm in diameter were studied histologically, morphometrically, radiographically and clinicopathologically in special reference to the stromal elastosis.

We classified PLA mto two types from the stromal elastotic framework (FFW). Type 1(24 patients) had the preserved EFW consisting of constantly thick stroma. Type 2 (182 patients) revealed the disrupted EFW especially in the center of tumor forming central fibrosis (CF) where many air spaces were collapsed or collagenized. At the periphery of type 2, extending stroma (Exst) was formed with thin walled elastic framework similar to normal alveoli (NA).

From the image analysis, increased amounts of elastic fibers could be calculated in type 1 ( 3.3-9.7 fold) and type 2 ( 3.9-7.6 fold) EFW compared to NA, which mean the contraction rate of pre-existing NA. In contrast, Exst in type 2 contained 0.8-2.1 fold of the fibers compared to NA suggesting mild-reacting pre-existing NA.

Radiographically, in type 1, tumor size hardly enlarged and the density tended to increase gradually over a long time. In type 2, tumor size tended to increase abruptly over a short time.

As prognosis of patients who were followed more than 3 years, 50% had relapsed in type 2, but none in type 1.

Conclusion ; Tumor stroma in the early stage of PLA might show the preserved EFW (type 1) formed by contractmg and thickening reaction of NA. As tumor developing, disrupted EFW (type 2) form CF with Exst. It indicate the stromal invasion and directly reflect to the prognosis.

153

CHRONIC INHALATION OF URBAN AMBIENT AIR INDU=s

MUl_TlF‘!CAL NEUROENWCRlNE CELL PAF’ILLOMAS AND

HYPERPLASIA IN THE RAT AIRWAY EF’ITHELIUM.

M. Kanisawa, T. Shibagaki, H. Kitamurrr. T- It%

Y. lnayama. wept. Path&, Yokohama City Univ. Schwa1 of

Medicine, Yokdaama, Japan. The real cause and pathogenesis of smal1 cell lung cancer

are still uncertain due to lacking of the proper animal

model. This paper reports chronic inhalation Of urban ambient air chiefly polluted with automobile exhaust gas

induces a high incidence of neuroendocrine cell PapillOmaS

and hyperplasia in the rat airway epithelium. Sixty-six male

Wistar rats were exposed to pollutd air in the animal

facilities installed on a street with heavy traffic in down-

tow” Yokohama. Nontreated control rats were bred in the

university aimal facilities is supplied Hepa-filtered air.

Densities of NOX. SOz axl dust particles were recorded

during the experment. Animals were sacrificed at the 26, 52

and 78 experimental weeks and the lungs were examined

histogically by serial sections. Production of multiple

papiliomas in the mid to small bronchi and foci of atypical cell hyperplasia mostly found in the bronchioli, particular-

ly in the brcnchio~oalveoIar region were frequently observed

in the rat exposed for 7X weeks. Certain “umber of the cells

composing these neoplastic lesion showed positive reaction

immtntohistochemically to calcitonine genera lated peptide

(CGRP). Development of the usual type of adenocarcinoma wz

found in 2 rats exposed for 78 weeks. Significant difference

between the inhaled air in both groups was detected only in

the contents of dust particles. These results may suggest urban ambient air densely polluted with dust particles

derived from automobile exhaust gas may be a possible cause of pulmonary neurcendacrine cell tumor in human.