1
338 Abstracts/Lung Cancer 13 (1995) 323-356 K-ras mutations in bronchoalveolar lavage fluid for diagnosing K-ras mutation-positive lung cancer were both 108%. For nine patients, K- ras mutations were detected in bnurchoalveolar lavage fluid obtained during otherwise nondiagnostic btonchoscopies. Conclusions: Gur data demonstrate that sensitive detection of K-ras codon 12 mutations can serve as an important af@mct to cytology in the diagnosis of lung cancer, Implicutions: Detection of these mutations could lead to earlier cancer diagnosis and less need for invasive diagnostic procedures P53 8ntibodies in the sera of lung cancer p8tientsz Comparison with p53 motation in the tumour tissue Wild CP, Bidanpaa M, Anttila S, Lubin K Soussi T. Husgafvel- Pursiainen K. Vainio H. URC, IS0 Cows Albert-Thomas, F69372 Lym Cedex a8. Int J Cancer 1995;64:176-81. This study examined the sensitivity and specificity of serum auto- antibodies to ~53 protein as a non-invasive marker of p53 genetic altcrati~r~~ or protein accumulation in lung cancer cases. A sensitive ELISA to detect serum p53 antibodies was developed and used to examine scra from 186 patients undergoing puhnonary surgery for a suspecd hmg cancer. Target antigens in ELISA were wild-type ~53 proteinand5peptidescoveringtbeN-andC-terminalI#lrtsofthe protein. Sixteen sera were positive for serum ~53 antibodies in both ELISAs and all were among the 136 patients with confirmed primary lung carcinoma. Gf 50 patients with other pulmonary diseases, none h&d ~53 antibodies. In 92 cancer patients exons 5 to 8 of the ~53 gene were examined for mutations by denaturing gradient gel electrophoresis and direct sequencing of PCB products. Forty-seven tumours had a ~53 mutation and 7 (15.2%) of these. were positive for ~53 antibodies. ‘Bvo patients had serum antibodies but no deteuable mutation in exons 5 to 8. FIUI~CS ofp53 mutations and senmr antibodies were higher in squamous cell carcinoma patients than in adenocarcinoma. Accumulation of ~53 protein in tumour tissue was observed in 32 patients, but only 5 were positive for p53 antibodies, In conclusion, Serum p53 aWodics wcrc Mectcd only in a proportion of lung cancer Cases,butthemajoritywuespeci6callyasmciatedwitharkectable p53 rnUtatiM ill the tlowor. Cyfra 21-1 as a biologic marker of non-small cell hag caocer: Evaluation of sensitivity, specificity, sod prognostic role Wieskopf B, Demangeat C, Purohit A, Stenger It, Gries P, Km&man H et al. Pavilion Luennec, I Place de I’Hopital, 67091 Strmbourg Cedex. Chest;1995:108/1 (163-169) Backgnwnd. C$Mc&ins are epithelial markers whose expression is nqt lost during malignant transformation. Cyfra 21-1 is a c@eratin- 19~thatissolublcinscnunudmaykausdulcirculMing tumormarla.~9obj~~ivc:Thtaimsdthirsadywat(l)toconfirm sensitivity and mpedcity of Cy6a 2 l-l in &ecting non-small cell lung canccr(NscLc)andupeciallythc ssuewrusctllsubtype,(2)toasscss thepotemialrelationshipbetweencyfra21-landdiseasestageofthe disuse in NSCLC. and (3) to evahmtc prognostic e&ct of Cylka 21-1 in NSCLC. Methodrz An immunoradiometric assay of serum Cyfra 2 l- 1wps~o~inl6lpatientswithlungcancerspnd71otberrwith benign lung diseasea. Tk ability of Cyba 21-1 to detect different histologiceubtypsoflungcancervsbcnignluclgdisascswasassessed th~~&receiveropwatingcbaractaistic(ROC)auvcsamtwmpnrisons with other tumor markers such as carcinoembryonic antigen neuron- spaifrc enolaae, and squamous cell carcinoma antigen. Comparisons of~21-1I~accordingtohistologicsubtypcanddisasestage were done using KNsI&W~U~~ teat. Mependent p.mgnostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox’s model). Results: Using a threshold of 3.3 n@L far Cyfra 21-1, sensitivity and spwificity were, rrqc&dy, 0.59 and 0.94 in NSCLC, 0.68 and 0.94 in the s&group of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-l levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations >32 ng/mL had stage IEB- IV and only one of I4 patients with stage I-II disease had Cyfm 21-l level >I8 ng/mL. In the multivariate analysis of survival, Qtiu 21-l was an independeut prognostic factor along with performance status and disu.w stage in NSCLC. Conclusions: Cyfra 21-l is a sensitive and specitic tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with per9ormam.e status and disease stage in N&C. Implications: A high level of Cyfra 21-l in apparently early- stage NSCLC should k an indication for more extensive workup before thoracotomy. The independent p~goostic role of Cyfia 21-l level may k us&d in stratitying populations with advanced NSCLC or early- stage msccted NSCLC as elevated Cyfra 21 -I levels might identify those patients at high risk for treatment failure. Serum level sod tissue expression of c-erbB-2 protein in lung adeooc8rcinom8 Osaki T, Mitswlomi T, Oyama T, Nakanishi R, Yasumoto K. Deportment of Swgety II, School ofMedicine. Univ. of Occapational/Envtl. Hlth.. I-I Iseigaoka. Yohatanishi-Ku. Kita@ushu 807. Chest 1995;lOS: l57- 62. Serum levels of ccrbB-2 protein were measured by an eoxyme immunoassay in 64 patients with lung adenocarcinoma. Immuno- histochemical staining was performed in 40 ofthese tumors. The mean se- concentration was 16.5i8.5 U/mL (range: 3.4 to 49.0) in patients with lung adenocarcinoma, wkreas it was 14.O~t3.7 U/mL (range: 6.9 to 20.9) in 15 controls (I U/mL=O.6 I ng/mL). Elevated concentrations ( 22.0 U/mL, control mean+2 SD) were observed in l7/64 lung adednoma patients (26.6%). as comptwalwith node ofthe control aubjccts @<o.OS). Patients with stage IIIB or T4 disease had increased serum levels. Tk senmt concentration was M significantlyby ugkal tumor ablation. Tissue -on was obtained in 17140 cases (42.540). and aem levels in patients with tissue overexpression wen higher than in patients without overexpression. Serum c-erbB-2 protein may k a useful indicator oftrmtor burden in patients with lung -mma. Invasion of tk tboracic wall io primmy long cancer ZaneniPP,SorisioV,~V,AmerioGM,CavaaenghiD,RmaGet al. Ospedale Civile, Via Borrallo. 14100 Asti. Minerva Chir 1994;49:1263-8. Theauthorsanalyseaserieaof5patientswhour&rwcntpulmonary andparietalnsedionbetweenl99oaodl993ductomn-microcytoma bronchogeniccarcinomawithinvasionofthethoracicwall. Thepatiuns wmpriscdfourmcnaadonewomanagedbetween45aad69yearsold. ThoNcic pain was present in two patients. Pulmonary resection with extrapleural stripping was performed in two Patients whereas a block resection from one to five ribs and the corresponding intercostal spacea was performed in the etkr three patients. The authors’ approach is not to perform these operations according to rigid pmtocols but to adapt them according to the local status of tumour invasion. Therefore to resort to extrapleural resection when there is a free cleavage plane ktweenparietalplauaandribwall;resection inblockdthewallwkre the carcinoma has intlltrated the endothoracic tkcia or dacpcr. The authors& notreportanymajordompkationsandmcordapostoperative mortality rate ofO%. In two cases the thomcic mall was recomnucted using a sheet of Gore-Tex which did not provoke rejection pknomena. Ftadiotherapy was carried out in cases with positive lymph nodes. The series presented here is too recent to provide significant data m8arding

P53 antibodies in the sera of lung cancer patients: Comparison with p53 mutation in the tumour tissue

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338 Abstracts/Lung Cancer 13 (1995) 323-356

K-ras mutations in bronchoalveolar lavage fluid for diagnosing K-ras mutation-positive lung cancer were both 108%. For nine patients, K- ras mutations were detected in bnurchoalveolar lavage fluid obtained during otherwise nondiagnostic btonchoscopies. Conclusions: Gur data demonstrate that sensitive detection of K-ras codon 12 mutations can serve as an important af@mct to cytology in the diagnosis of lung cancer, Implicutions: Detection of these mutations could lead to earlier cancer diagnosis and less need for invasive diagnostic procedures

P53 8ntibodies in the sera of lung cancer p8tientsz Comparison with p53 motation in the tumour tissue Wild CP, Bidanpaa M, Anttila S, Lubin K Soussi T. Husgafvel- Pursiainen K. Vainio H. URC, IS0 Cows Albert-Thomas, F69372 Lym Cedex a8. Int J Cancer 1995;64:176-81.

This study examined the sensitivity and specificity of serum auto- antibodies to ~53 protein as a non-invasive marker of p53 genetic altcrati~r~~ or protein accumulation in lung cancer cases. A sensitive ELISA to detect serum p53 antibodies was developed and used to examine scra from 186 patients undergoing puhnonary surgery for a suspecd hmg cancer. Target antigens in ELISA were wild-type ~53 proteinand5peptidescoveringtbeN-andC-terminalI#lrtsofthe protein. Sixteen sera were positive for serum ~53 antibodies in both ELISAs and all were among the 136 patients with confirmed primary lung carcinoma. Gf 50 patients with other pulmonary diseases, none h&d ~53 antibodies. In 92 cancer patients exons 5 to 8 of the ~53 gene were examined for mutations by denaturing gradient gel electrophoresis and direct sequencing of PCB products. Forty-seven tumours had a ~53 mutation and 7 (15.2%) of these. were positive for ~53 antibodies. ‘Bvo patients had serum antibodies but no deteuable mutation in exons 5 to 8. FIUI~CS ofp53 mutations and senmr antibodies were higher in squamous cell carcinoma patients than in adenocarcinoma. Accumulation of ~53 protein in tumour tissue was observed in 32 patients, but only 5 were positive for p53 antibodies, In conclusion, Serum p53 aWodics wcrc Mectcd only in a proportion of lung cancer Cases,butthemajoritywuespeci6callyasmciatedwitharkectable p53 rnUtatiM ill the tlowor.

Cyfra 21-1 as a biologic marker of non-small cell hag caocer: Evaluation of sensitivity, specificity, sod prognostic role Wieskopf B, Demangeat C, Purohit A, Stenger It, Gries P, Km&man H et al. Pavilion Luennec, I Place de I’Hopital, 67091 Strmbourg Cedex. Chest;1995:108/1 (163-169)

Backgnwnd. C$Mc&ins are epithelial markers whose expression is nqt lost during malignant transformation. Cyfra 21-1 is a c@eratin- 19~thatissolublcinscnunudmaykausdulcirculMing tumormarla.~9obj~~ivc:Thtaimsdthirsadywat(l)toconfirm sensitivity and mpedcity of Cy6a 2 l-l in &ecting non-small cell lung canccr(NscLc)andupeciallythc ssuewrusctllsubtype,(2)toasscss thepotemialrelationshipbetweencyfra21-landdiseasestageofthe disuse in NSCLC. and (3) to evahmtc prognostic e&ct of Cylka 21-1 in NSCLC. Methodrz An immunoradiometric assay of serum Cyfra 2 l- 1wps~o~inl6lpatientswithlungcancerspnd71otberrwith benign lung diseasea. Tk ability of Cyba 21-1 to detect different histologiceubtypsoflungcancervsbcnignluclgdisascswasassessed th~~&receiveropwatingcbaractaistic(ROC)auvcsamtwmpnrisons with other tumor markers such as carcinoembryonic antigen neuron- spaifrc enolaae, and squamous cell carcinoma antigen. Comparisons of~21-1I~accordingtohistologicsubtypcanddisasestage were done using KNsI&W~U~~ teat. Mependent p.mgnostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox’s model). Results: Using a threshold of 3.3 n@L far Cyfra 21-1, sensitivity and spwificity were, rrqc&dy, 0.59 and 0.94 in NSCLC,

0.68 and 0.94 in the s&group of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-l levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations >32 ng/mL had stage IEB- IV and only one of I4 patients with stage I-II disease had Cyfm 21-l level >I8 ng/mL. In the multivariate analysis of survival, Qtiu 21-l was an independeut prognostic factor along with performance status and disu.w stage in NSCLC. Conclusions: Cyfra 21-l is a sensitive and specitic tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with per9ormam.e status and disease stage in N&C. Implications: A high level of Cyfra 21-l in apparently early- stage NSCLC should k an indication for more extensive workup before thoracotomy. The independent p~goostic role of Cyfia 21-l level may k us&d in stratitying populations with advanced NSCLC or early- stage msccted NSCLC as elevated Cyfra 21 -I levels might identify those patients at high risk for treatment failure.

Serum level sod tissue expression of c-erbB-2 protein in lung adeooc8rcinom8 Osaki T, Mitswlomi T, Oyama T, Nakanishi R, Yasumoto K. Deportment of Swgety II, School ofMedicine. Univ. of Occapational/Envtl. Hlth.. I-I Iseigaoka. Yohatanishi-Ku. Kita@ushu 807. Chest 1995;lOS: l57- 62.

Serum levels of ccrbB-2 protein were measured by an eoxyme immunoassay in 64 patients with lung adenocarcinoma. Immuno- histochemical staining was performed in 40 ofthese tumors. The mean se- concentration was 16.5i8.5 U/mL (range: 3.4 to 49.0) in patients with lung adenocarcinoma, wkreas it was 14.O~t3.7 U/mL (range: 6.9 to 20.9) in 15 controls (I U/mL=O.6 I ng/mL). Elevated concentrations ( 22.0 U/mL, control mean+2 SD) were observed in l7/64 lung adednoma patients (26.6%). as comptwalwith node ofthe control aubjccts @<o.OS). Patients with stage IIIB or T4 disease had increased serum levels. Tk senmt concentration was M significantlyby ugkal tumor ablation. Tissue -on was obtained in 17140 cases (42.540). and aem levels in patients with tissue overexpression wen higher than in patients without overexpression. Serum c-erbB-2 protein may k a useful indicator oftrmtor burden in patients with lung -mma.

Invasion of tk tboracic wall io primmy long cancer ZaneniPP,SorisioV,~V,AmerioGM,CavaaenghiD,RmaGet al. Ospedale Civile, Via Borrallo. 14100 Asti. Minerva Chir 1994;49:1263-8.

Theauthorsanalyseaserieaof5patientswhour&rwcntpulmonary andparietalnsedionbetweenl99oaodl993ductomn-microcytoma bronchogeniccarcinomawithinvasionofthethoracicwall. Thepatiuns wmpriscdfourmcnaadonewomanagedbetween45aad69yearsold. ThoNcic pain was present in two patients. Pulmonary resection with extrapleural stripping was performed in two Patients whereas a block resection from one to five ribs and the corresponding intercostal spacea was performed in the etkr three patients. The authors’ approach is not to perform these operations according to rigid pmtocols but to adapt them according to the local status of tumour invasion. Therefore to resort to extrapleural resection when there is a free cleavage plane ktweenparietalplauaandribwall;resection inblockdthewallwkre the carcinoma has intlltrated the endothoracic tkcia or dacpcr. The authors& notreportanymajordompkationsandmcordapostoperative mortality rate ofO%. In two cases the thomcic mall was recomnucted using a sheet of Gore-Tex which did not provoke rejection pknomena. Ftadiotherapy was carried out in cases with positive lymph nodes. The series presented here is too recent to provide significant data m8arding