angiogenesis and molecular biologic substaging in patients with stage i non-small cell lung cancer

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116 Abstracts / Lung Cancer 16 (1996) 105-127 In the period of 25 years authors observed in the I. Clinic for TB and Pulmonary Diseases in Prague 28 patients with the diagnosis of bronchioloalveolar carcinoma. This group consisted from 17 female and 11 male patients with an average age of 58.6 years. ?ivo patients had a risk. working in an uranium mine, 15 were non-smokers. 5 pa- tients had no clinical symptoms, 12 suffered from cough and chest pain, 7 had breathlessness, 2 had weight loss and other 2 patients had hemoptysis. Authors verified the diagnosis by histologic examination of resecates (13 times), from the tissues withdrawn by biopsy (3 times). and from material obtained by autopsy (2 times). Cytologic diagnostics was made in total IO times from material obtained during bronchos- copy. bronchoalveolar lavage and from lung puncture. 13 patients un- derwent surgical treatment, 4 of them survive (2, 3, 7 and 22 years) after operation. In total 20 patients died during two years, all of them were dissected and in 12 cases generalisation of the tumour was found. Fine-needle aspiration as the initial diagnostic modality in ma- lignant lung disease Blumenfeld W, Singer M, Glanz S, Hon M. Department of Pathology Winthrop-University Hospital, 222 Station Plaza North, Mineola, N? 11501. Diagn Cytopathol 1996;14:268-72. Cytologic detection of lung cancer is accepted, accurate, and time- honored. Typically, cytologic workup of a radiologic abnormality pro- ceeds sequentially from sputum to bronchoalveolar cytology, and, if necessary, to tine-needle aspiration biopsy @HA). Initial use of FNA in lung cancer diagnosis is controversial, but increasingly popular. We therefore decided to objectively assess current practice in cytologic lung cancer diagnosis at our institution. All pulmonary cytologic diagnoses for 1993 and the first half of 1994 were retrieved. Positive diagnoses were then used to access all patient data. Patients were stratified ac- cording to the specimen from which the first positive diagnosis was obtained, Of 542 pulmonary cytology specimens, 15% were sputa. 65% were bronchoalveolar. and 20% were FNAs. One hundred sixty- one of 172 malignant diagnoses were first diagnoses. Three percent of first malignant diagnoses were made from sputa, 47% were from lavages. and 50% were from FNAs. Although PNAs comprised just 20% of all pulmonary cytologies. 50% of all new malignant cytologic diagnoses were made by PNA. Initial use of FNA is successful, has a high diag- nostic yield and low complication rate. and offers the most direct ap- proach to diagnosis. Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer Harpole DH, Richards WG, Hemdon II JE, Sugarbaker DJ. Divisron of Thoracic Surgery, Duke Universily Medical Center, PO Box 3617, Durham, NC 27710. Ami Thorac Surg 1996;61:1470-6. Background. Although complete surgical resection remains the pri- mary treatment for localized stage I non-small cell lung cancer, the cancer recurrence rate is 25% to 40%. If one could identity a subset of patients using molecular factors that contribute to tumor aggressive- ness, one might improve prognosis in this group with additional treat- ment. High expression of angiogenesis factor viii has been associated with the presence of nodal metastases in breast cancer; here we exam- ined its relation to survival with non-small cell lung cancer. Methods. We examined angiogenesis using immunohistochemistry on parathn blocks of tumor from 275 consecutive patients with stage I non-small cell lung cancer, more than 68 months of follow-up, and a 64% 5-year survival. Angiogenesis was calculated from the microvessel number per ten 200 x microscope fields measured at the tumor periphery, in the center, and in the area of highest concentration. Results. Measurements in the central area were inconsistent due to prominent necrosis. How- ever. microvessel number recorded at the periphery and at the ‘hottest’ area correlated well (r’ = 0.952, p = 0.001). and a significant survival advantage was noted for low-level expression at both areas (peripheral, p = 0.046; ‘hottest’, p = 0.006). Multivariate survival analysis using angiogenesis, protooncogene erbB-2, tumor suppressor gene ~53, and the proliferation marker KI-67 defined angiogenesis as the most sig- nificant prognostic factor in stage I hmg cancer. Conclusions. This molecular biologic substaging system including angiogenesis for stage I non-small cell lung cancer is independent of routine histopathologic factors and revealed an additive adverse effect with expression of sev- eral biologic markers (5-year survival: no marker [n = 51]81%, 1 marker [n = 821 71%, 2 markers [n = 841 54%, and 3 to 4 markers [n = 581 49%; p = 0.0001). Ultrasound-guided fine-needle aspiration biopsy of lung can- cers Hsu WH, Chiang CD, Hsu JY, Kwan PC, Chen CL, Chen CY. Division of Chest Medicine. Department of Internal Medicine, Taichung Veter- ans General Hospital, Taichung. J Clin Ultrasound 1996;24: 225-33. One hundred eighty-eight patients with 191 lung cancers werecollected retrospectively to evaluate the diagnostic results and to determine the accuracy of cytologic diagnoses obtained from ultrasound- guided tine-needle aspiration biopsy (US-guided FNAB), and to dis- cuss the necessity of large-bore tissue core needle biopsy. All 188 pa- tients underwent US-guided FNAB, and 20 patients with 2 1 lung tumors also underwent US-guided tissue-core needle biopsy. Using US-guided FNAEl alone, the positive cytologic results and correct cytologic diag- noses were 91% (174 of 191) and 71% (37 of 52). If both US-guided PNAB and selected US-guided tissue core needle biopsy (n = 21) were evaluated, the positive cytologic or histologic results and correct cytologic or histologic diagnoses were 94% (180 of 191) and 80% (45 of 57). respectively. Analyzing the disagreement between the cytologic results and histologic diagnoses (n = 15). we found that the disagreement usu- ally occurred in the specimens with poorly differentiated carcinomas (nonspecific cell type) (53% [8 of 151); of these. two patients (13% 12 of 151, small cell carcinoma) would have a change in treatment. The complications of US-guided FNAB were pneumothorax (n = 3). hemoptysis (n = l), hemothorax (n = I), and suspected tract metastasis (n = I). We conclude that US-guided FNAB has a high diagnostic yield in lung cancers, and US-guided tissue core needle biopsy is only neces- sary in patients whose cytologic results are negative or who have poorly differentiated carcinomas. Prognostic value of MIB-1 in neuroendocrine turnout-s of the lung Bohm I, Koch S, Gais P, Jutting U, Prauer HW, Hofler H. Institute of Pathology, Technical Unwersrty ofMunich, lsmaninger St,: 22, 81675 Munich. J Pathol 1996; 178:402-9. The spectrum of neuroendocrine lung tumours ranges from highly aggressive small cell carcinomas (SCLC) to carcinoid tumours (CD) of low malignant potential. Between these two extremes, the ‘well-differ- entiated neuroendocrine carcinomas’ CWDNEC) form a transitional group with uncertain biological behaviour. This study investigated the prognostic value of the proliferation marker MIB-I (paraffin Ki-67) in 59 neuroendocrine lung tumours (32 SCLC, 13 WDNEC, 14 CD) by immunostaining of routinely processed paraftIn sections, Morphometric evaluation was done by semi-automatic image analysis. The results were compared with survival data (mean follow-up: 42 months). The prolif- eration rates of the tumours as determined by MIB-1 immunoreactivity (MIB-I-PR) were significantly different between the tumour types (SCLC>WDNECXD) and showed a strong inverse correlation with survival time. In CD, the percentage of MIB-1-labelled nuclei never exceeded 1.1 per cent; higher values would therefore favour the diag- nosis of WDNEC over that of CD. Among WDNEC, MIB- 1 was able to differentiate a subgroup with excellent prognosis (MIB-I-PR: 0.3-3.4

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Page 1: Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer

116 Abstracts / Lung Cancer 16 (1996) 105-127

In the period of 25 years authors observed in the I. Clinic for TB and Pulmonary Diseases in Prague 28 patients with the diagnosis of bronchioloalveolar carcinoma. This group consisted from 17 female and 11 male patients with an average age of 58.6 years. ?ivo patients had a risk. working in an uranium mine, 15 were non-smokers. 5 pa- tients had no clinical symptoms, 12 suffered from cough and chest pain, 7 had breathlessness, 2 had weight loss and other 2 patients had hemoptysis. Authors verified the diagnosis by histologic examination of resecates (13 times), from the tissues withdrawn by biopsy (3 times). and from material obtained by autopsy (2 times). Cytologic diagnostics was made in total IO times from material obtained during bronchos- copy. bronchoalveolar lavage and from lung puncture. 13 patients un- derwent surgical treatment, 4 of them survive (2, 3, 7 and 22 years) after operation. In total 20 patients died during two years, all of them were dissected and in 12 cases generalisation of the tumour was found.

Fine-needle aspiration as the initial diagnostic modality in ma- lignant lung disease Blumenfeld W, Singer M, Glanz S, Hon M. Department of Pathology Winthrop-University Hospital, 222 Station Plaza North, Mineola, N? 11501. Diagn Cytopathol 1996;14:268-72.

Cytologic detection of lung cancer is accepted, accurate, and time- honored. Typically, cytologic workup of a radiologic abnormality pro- ceeds sequentially from sputum to bronchoalveolar cytology, and, if necessary, to tine-needle aspiration biopsy @HA). Initial use of FNA in lung cancer diagnosis is controversial, but increasingly popular. We therefore decided to objectively assess current practice in cytologic lung cancer diagnosis at our institution. All pulmonary cytologic diagnoses for 1993 and the first half of 1994 were retrieved. Positive diagnoses were then used to access all patient data. Patients were stratified ac- cording to the specimen from which the first positive diagnosis was obtained, Of 542 pulmonary cytology specimens, 15% were sputa. 65% were bronchoalveolar. and 20% were FNAs. One hundred sixty- one of 172 malignant diagnoses were first diagnoses. Three percent of first malignant diagnoses were made from sputa, 47% were from lavages. and 50% were from FNAs. Although PNAs comprised just 20% of all pulmonary cytologies. 50% of all new malignant cytologic diagnoses were made by PNA. Initial use of FNA is successful, has a high diag- nostic yield and low complication rate. and offers the most direct ap- proach to diagnosis.

Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer Harpole DH, Richards WG, Hemdon II JE, Sugarbaker DJ. Divisron of Thoracic Surgery, Duke Universily Medical Center, PO Box 3617, Durham, NC 27710. Ami Thorac Surg 1996;61:1470-6.

Background. Although complete surgical resection remains the pri- mary treatment for localized stage I non-small cell lung cancer, the cancer recurrence rate is 25% to 40%. If one could identity a subset of patients using molecular factors that contribute to tumor aggressive- ness, one might improve prognosis in this group with additional treat- ment. High expression of angiogenesis factor viii has been associated with the presence of nodal metastases in breast cancer; here we exam-

ined its relation to survival with non-small cell lung cancer. Methods. We examined angiogenesis using immunohistochemistry on parathn blocks of tumor from 275 consecutive patients with stage I non-small cell lung cancer, more than 68 months of follow-up, and a 64% 5-year survival. Angiogenesis was calculated from the microvessel number per ten 200 x microscope fields measured at the tumor periphery, in the center, and in the area of highest concentration. Results. Measurements in the central area were inconsistent due to prominent necrosis. How- ever. microvessel number recorded at the periphery and at the ‘hottest’ area correlated well (r’ = 0.952, p = 0.001). and a significant survival

advantage was noted for low-level expression at both areas (peripheral, p = 0.046; ‘hottest’, p = 0.006). Multivariate survival analysis using angiogenesis, protooncogene erbB-2, tumor suppressor gene ~53, and the proliferation marker KI-67 defined angiogenesis as the most sig- nificant prognostic factor in stage I hmg cancer. Conclusions. This molecular biologic substaging system including angiogenesis for stage I non-small cell lung cancer is independent of routine histopathologic factors and revealed an additive adverse effect with expression of sev-

eral biologic markers (5-year survival: no marker [n = 51]81%, 1 marker [n = 821 71%, 2 markers [n = 841 54%, and 3 to 4 markers [n = 581 49%; p = 0.0001).

Ultrasound-guided fine-needle aspiration biopsy of lung can- cers Hsu WH, Chiang CD, Hsu JY, Kwan PC, Chen CL, Chen CY. Division of Chest Medicine. Department of Internal Medicine, Taichung Veter- ans General Hospital, Taichung. J Clin Ultrasound 1996;24: 225-33.

One hundred eighty-eight patients with 191 lung cancers werecollected retrospectively to evaluate the diagnostic results and to determine the accuracy of cytologic diagnoses obtained from ultrasound- guided tine-needle aspiration biopsy (US-guided FNAB), and to dis- cuss the necessity of large-bore tissue core needle biopsy. All 188 pa- tients underwent US-guided FNAB, and 20 patients with 2 1 lung tumors also underwent US-guided tissue-core needle biopsy. Using US-guided FNAEl alone, the positive cytologic results and correct cytologic diag- noses were 91% (174 of 191) and 71% (37 of 52). If both US-guided PNAB and selected US-guided tissue core needle biopsy (n = 21) were evaluated, the positive cytologic or histologic results and correct cytologic or histologic diagnoses were 94% (180 of 191) and 80% (45 of 57). respectively. Analyzing the disagreement between the cytologic results and histologic diagnoses (n = 15). we found that the disagreement usu- ally occurred in the specimens with poorly differentiated carcinomas (nonspecific cell type) (53% [8 of 151); of these. two patients (13% 12 of 151, small cell carcinoma) would have a change in treatment. The complications of US-guided FNAB were pneumothorax (n = 3). hemoptysis (n = l), hemothorax (n = I), and suspected tract metastasis (n = I). We conclude that US-guided FNAB has a high diagnostic yield in lung cancers, and US-guided tissue core needle biopsy is only neces- sary in patients whose cytologic results are negative or who have poorly differentiated carcinomas.

Prognostic value of MIB-1 in neuroendocrine turnout-s of the lung Bohm I, Koch S, Gais P, Jutting U, Prauer HW, Hofler H. Institute of Pathology, Technical Unwersrty ofMunich, lsmaninger St,: 22, 81675 Munich. J Pathol 1996; 178:402-9.

The spectrum of neuroendocrine lung tumours ranges from highly aggressive small cell carcinomas (SCLC) to carcinoid tumours (CD) of low malignant potential. Between these two extremes, the ‘well-differ- entiated neuroendocrine carcinomas’ CWDNEC) form a transitional group with uncertain biological behaviour. This study investigated the prognostic value of the proliferation marker MIB-I (paraffin Ki-67) in 59 neuroendocrine lung tumours (32 SCLC, 13 WDNEC, 14 CD) by immunostaining of routinely processed paraftIn sections, Morphometric evaluation was done by semi-automatic image analysis. The results were compared with survival data (mean follow-up: 42 months). The prolif- eration rates of the tumours as determined by MIB-1 immunoreactivity (MIB-I-PR) were significantly different between the tumour types (SCLC>WDNECXD) and showed a strong inverse correlation with survival time. In CD, the percentage of MIB-1-labelled nuclei never exceeded 1.1 per cent; higher values would therefore favour the diag- nosis of WDNEC over that of CD. Among WDNEC, MIB- 1 was able to differentiate a subgroup with excellent prognosis (MIB-I-PR: 0.3-3.4