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Angiogenesis: An indicator of metastasis in non-small cell lung cancer invading the thoracic inlet
Abstracts/Lung
Cancer
signiticance of these three cytokeratin markers in lung cancer and in carcinoma of the urinary bladder. For Uris purpose we investigated the sera of 50 healthy persons, 273 patients with various benign diseases, 218 patients with histologically proven lung cancer and 88 patients with carcinoma of the urinary bladder. In a first step the specificity was established for the diRerent reference groups and the cutoff values were fixed at a specificity of 95%. In lung cancer the single and combined sensitivities were calculated versus benign lung diseases (n = 58) as reference group. With single determinations CYFIU 21-1 proved to have the highest sensitivity in lung cancer in general (61%) in nonsmall cell lung carcinomas (640/o), in squamous cell carcinomas (79%). in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas (SCLC) NSE was confirmed to be the marker of choice (55%). With combined determinations a clear increase in sensitivity could only be reached in large cell carcinomas (CYFRA 211 + TPA: 77%) and in small cell carcinomas (CYFRA 21-1 + NSE: 62%). In cancer of the urinary bladder the sensitivities were established versus benign urological diseases (n = 73). CYFRA 21-I showed with 38% tme positive test results the highest sensitivity compared to TPA (27%) and TPS (23%). From our investigations it was evident that TPA detects at least partially the same substance as CYFRA 21-l (the sensitivities compared to the markers TPS, CEA, SCC and NSE were rather high, but not as high as for CYFRA 2 1-1) whereas TPS represents a completely different parameter of clinical chemistry (lowest number of true positive test results over the whole investigation), which apparently measures something completely different. These. findings cleary correspond with the very recent results of immunoblotting comparing CYFRA 21-1, TPA and TPS.
Significance of the dosage of plasma carcinocmbtyonic antigen in small cell carcinoma Michetti G, Bamberga M, Pugliese C, C&i Belometti M, Amone P, Mini0 A et a~. Ma Coghetti, 218.24128Betgamo. Minerva Med 1994;85:23 l6. The clinical value of the serum biomarker carcinoembtyonic antigen (CEA) was evaluated prospectively in 118 patients with small cell lung cancer (SCLC) entered chemotherapy protocol between 1986 and 1992. Five quantitative categories were determined: less than 2.5 @ml and 2.6-5.0 nghl (the standard normal), 5.1-20.0 ng/mL 20.1-100 rig/ml and greater than 100 rig/ml. 70% of patients had Iweb less than 5 ng/ ml and oniy 19% had levels greater than 20 ng/&. There was no dearcUt relationship of plasma CEA level to stage of disease, in which 61% of patients with extensive disease (59 patients) had levels less than 5 npl ml and 22% of patients with limited disease (59 patients) had levels greater than 5 @ml. There was a modest relationship of CEA levels tn presence of mebmtases, in that 50% of patients with me&stases had levds greater than 20 rig/ml. The average survival for the pathologic and normal category was almost similar, ranging Ram 13.27 to 16.81 months. The correlation between disease extent and survival was more sensitive for lactate dehydrogenase (LDH) than for CEA. So CEA as a tumor marker for SCLC must’be applied in Eonjunction with other biomarkets, particularly LDH and neuron speciiic enolase (NSE) and is meaningful in only a small proportion of patients.
Sex hormone receptors in non-small-cell longcanccr in human beiigs Canver CC, Memoli VA, Vandeneer PL, Dingivan CA, Mentzer RM Jr. Division of Caniiothoracic Surgery, 114/352 CIinical Science Cente,: Nkonsin Univ. -bfadison Medical Sch., 600 HighlandAve., Madison, W53792. J Thorac Cardiovasc Surg 1994;108:153-7. To investigate whether sex hormone receptors exist in the resected nonsmall-cell lung cancer in humanbeings and to determine a linkbetween
I2 (1995)
113-160
135
the ptdmonary carcinogenesis and the sex receptor status of the lung cancer tissue, we reviewed the case histories of 64 patients who underwent resectional therapy for non-small-cell lung cancer between 1988 and 1990 (38 men and 26 women, mean age 65 years). Mouse monoclonal immunoglobtdin G antibodies were used for immunohistochemical detection of estrogen receptors and progesterone receptors in the acetone-fixed specimen. The control group consisted ofnormal lung tissue from the patients with and without bronchogenic carcinoma and breast cancer tissue from the patients with estrogen and progesterone receptor immunoreactivity. No evidence of estrogen and progesterone receptor immunoreactivity was present in the normal lung tissue. AR but two patients had immunoreactivity (97%) for estrogen receptors in the lung cancer tissue @ < 0.001). Immunoreactivity for progesterone receptors was absent or weak in the majority @ > 0.05). The differences for sex and for histologic subtypes were not statistically signiticant. Obsc~ed actuarial survival at 3 years was 83% for all patients with estrogen receptor immtmoreactivity: 94% for women and 75% for men @ < 0.05). We found no correlation between the hormone receptor status and the type, clinical features, or prognosis of the non-small-cell lung cancer. We conclude that an abundance of estrogen receptors is hosted only in cancerous tissue, not in normal pulmonary tissue. Improved identification and definition of estrogen receptors in the nontarget lung cancer tissue offer a possibility of antiestrogen therapy for patients with advanced bmnchogenic carcinoma. Angiogenesis: An indicator of metastasis in non-small cell lung cancer invading the thorncic inlet Macchiarini P, Fontanini G, Dulmet E, De Montpreville V, Chapelier AR, Cenina J et al. Dept. of ThoracicNnscular Surgery, HopitalMarieLmnelongue, Paris&d University, 133, Avenue de la Resistance, 92350 Plessis Robinson. Ann Thorac Surg 1994;57:1534-9. We have attempted to identify a biologic rationale for the local aggressiveness and late treatment failure of resected non-small cell lung cancer involving the thoracic inlet. Tumor specimens from 28 patients who underwent a new transcervical approach were analyzed for the expression of tumor proliferative activity, suppressor-gene ~53, intratumoral and peritumoral blood vessel invasion by tumor cells, the presence and degree of angiogenesis (induction of new capillaries and venules), and other biologic variables. Eighty-nine percent of the neoplasms were moderately or poorly differentiated, 89% expressed either an intermediate or high proliferative activity, 39% showed ~53 aberrations, 71% exhibited induction of angiogenesis, and 39% had tumors that were positive for blood vessel invasion. With a median follow-up time of 3.5 years (range, 8 to 145+ months), the overall projected 5-year survival was 29%and the median disease-tree interval was 23 months. Results of univariate and multivariate analysis of survival and the disease-free interval identified the degree of angiogenesis (density less than 1 versus more than 1 and number of neovessels less than 6 versus more than 6) as the only independent and signiticant predictors of the disease-free interval. Patients whose tumor showed a density of angiogenesis of 1 or greater and a number of neovessels of 6 or greater faced a significantly @ = 0.0001) higher relative risk of suffering systemic recurrence of their primary tumor than did their low-risk counterparts. Results demonstrate that angiogenesis significantly correlates with late treatment failure (metastasis), and this is acquired at a critical density and number of vessels. Prognostic factors for survival in terminal lung cancer patients Schonwetter RS, Robinson BE, Ramirez G. Division of Geriatric Medicine. Deparhmnt ofInternaIMedicine, South Florida Univ. Coil. ofMed.. 12901 Bruce B. Downs Boulevmi, Tampa, FL 33612. J Gen Intern Med 1994;9:366-71.
Cancer
signiticance of these three cytokeratin markers in lung cancer and in carcinoma of the urinary bladder. For Uris purpose we investigated the sera of 50 healthy persons, 273 patients with various benign diseases, 218 patients with histologically proven lung cancer and 88 patients with carcinoma of the urinary bladder. In a first step the specificity was established for the diRerent reference groups and the cutoff values were fixed at a specificity of 95%. In lung cancer the single and combined sensitivities were calculated versus benign lung diseases (n = 58) as reference group. With single determinations CYFIU 21-1 proved to have the highest sensitivity in lung cancer in general (61%) in nonsmall cell lung carcinomas (640/o), in squamous cell carcinomas (79%). in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas (SCLC) NSE was confirmed to be the marker of choice (55%). With combined determinations a clear increase in sensitivity could only be reached in large cell carcinomas (CYFRA 211 + TPA: 77%) and in small cell carcinomas (CYFRA 21-1 + NSE: 62%). In cancer of the urinary bladder the sensitivities were established versus benign urological diseases (n = 73). CYFRA 21-I showed with 38% tme positive test results the highest sensitivity compared to TPA (27%) and TPS (23%). From our investigations it was evident that TPA detects at least partially the same substance as CYFRA 21-l (the sensitivities compared to the markers TPS, CEA, SCC and NSE were rather high, but not as high as for CYFRA 2 1-1) whereas TPS represents a completely different parameter of clinical chemistry (lowest number of true positive test results over the whole investigation), which apparently measures something completely different. These. findings cleary correspond with the very recent results of immunoblotting comparing CYFRA 21-1, TPA and TPS.
Significance of the dosage of plasma carcinocmbtyonic antigen in small cell carcinoma Michetti G, Bamberga M, Pugliese C, C&i Belometti M, Amone P, Mini0 A et a~. Ma Coghetti, 218.24128Betgamo. Minerva Med 1994;85:23 l6. The clinical value of the serum biomarker carcinoembtyonic antigen (CEA) was evaluated prospectively in 118 patients with small cell lung cancer (SCLC) entered chemotherapy protocol between 1986 and 1992. Five quantitative categories were determined: less than 2.5 @ml and 2.6-5.0 nghl (the standard normal), 5.1-20.0 ng/mL 20.1-100 rig/ml and greater than 100 rig/ml. 70% of patients had Iweb less than 5 ng/ ml and oniy 19% had levels greater than 20 ng/&. There was no dearcUt relationship of plasma CEA level to stage of disease, in which 61% of patients with extensive disease (59 patients) had levels less than 5 npl ml and 22% of patients with limited disease (59 patients) had levels greater than 5 @ml. There was a modest relationship of CEA levels tn presence of mebmtases, in that 50% of patients with me&stases had levds greater than 20 rig/ml. The average survival for the pathologic and normal category was almost similar, ranging Ram 13.27 to 16.81 months. The correlation between disease extent and survival was more sensitive for lactate dehydrogenase (LDH) than for CEA. So CEA as a tumor marker for SCLC must’be applied in Eonjunction with other biomarkets, particularly LDH and neuron speciiic enolase (NSE) and is meaningful in only a small proportion of patients.
Sex hormone receptors in non-small-cell longcanccr in human beiigs Canver CC, Memoli VA, Vandeneer PL, Dingivan CA, Mentzer RM Jr. Division of Caniiothoracic Surgery, 114/352 CIinical Science Cente,: Nkonsin Univ. -bfadison Medical Sch., 600 HighlandAve., Madison, W53792. J Thorac Cardiovasc Surg 1994;108:153-7. To investigate whether sex hormone receptors exist in the resected nonsmall-cell lung cancer in humanbeings and to determine a linkbetween
I2 (1995)
113-160
135
the ptdmonary carcinogenesis and the sex receptor status of the lung cancer tissue, we reviewed the case histories of 64 patients who underwent resectional therapy for non-small-cell lung cancer between 1988 and 1990 (38 men and 26 women, mean age 65 years). Mouse monoclonal immunoglobtdin G antibodies were used for immunohistochemical detection of estrogen receptors and progesterone receptors in the acetone-fixed specimen. The control group consisted ofnormal lung tissue from the patients with and without bronchogenic carcinoma and breast cancer tissue from the patients with estrogen and progesterone receptor immunoreactivity. No evidence of estrogen and progesterone receptor immunoreactivity was present in the normal lung tissue. AR but two patients had immunoreactivity (97%) for estrogen receptors in the lung cancer tissue @ < 0.001). Immunoreactivity for progesterone receptors was absent or weak in the majority @ > 0.05). The differences for sex and for histologic subtypes were not statistically signiticant. Obsc~ed actuarial survival at 3 years was 83% for all patients with estrogen receptor immtmoreactivity: 94% for women and 75% for men @ < 0.05). We found no correlation between the hormone receptor status and the type, clinical features, or prognosis of the non-small-cell lung cancer. We conclude that an abundance of estrogen receptors is hosted only in cancerous tissue, not in normal pulmonary tissue. Improved identification and definition of estrogen receptors in the nontarget lung cancer tissue offer a possibility of antiestrogen therapy for patients with advanced bmnchogenic carcinoma. Angiogenesis: An indicator of metastasis in non-small cell lung cancer invading the thorncic inlet Macchiarini P, Fontanini G, Dulmet E, De Montpreville V, Chapelier AR, Cenina J et al. Dept. of ThoracicNnscular Surgery, HopitalMarieLmnelongue, Paris&d University, 133, Avenue de la Resistance, 92350 Plessis Robinson. Ann Thorac Surg 1994;57:1534-9. We have attempted to identify a biologic rationale for the local aggressiveness and late treatment failure of resected non-small cell lung cancer involving the thoracic inlet. Tumor specimens from 28 patients who underwent a new transcervical approach were analyzed for the expression of tumor proliferative activity, suppressor-gene ~53, intratumoral and peritumoral blood vessel invasion by tumor cells, the presence and degree of angiogenesis (induction of new capillaries and venules), and other biologic variables. Eighty-nine percent of the neoplasms were moderately or poorly differentiated, 89% expressed either an intermediate or high proliferative activity, 39% showed ~53 aberrations, 71% exhibited induction of angiogenesis, and 39% had tumors that were positive for blood vessel invasion. With a median follow-up time of 3.5 years (range, 8 to 145+ months), the overall projected 5-year survival was 29%and the median disease-tree interval was 23 months. Results of univariate and multivariate analysis of survival and the disease-free interval identified the degree of angiogenesis (density less than 1 versus more than 1 and number of neovessels less than 6 versus more than 6) as the only independent and signiticant predictors of the disease-free interval. Patients whose tumor showed a density of angiogenesis of 1 or greater and a number of neovessels of 6 or greater faced a significantly @ = 0.0001) higher relative risk of suffering systemic recurrence of their primary tumor than did their low-risk counterparts. Results demonstrate that angiogenesis significantly correlates with late treatment failure (metastasis), and this is acquired at a critical density and number of vessels. Prognostic factors for survival in terminal lung cancer patients Schonwetter RS, Robinson BE, Ramirez G. Division of Geriatric Medicine. Deparhmnt ofInternaIMedicine, South Florida Univ. Coil. ofMed.. 12901 Bruce B. Downs Boulevmi, Tampa, FL 33612. J Gen Intern Med 1994;9:366-71.