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p53 and disease progression in patients with non-small cell lung cancer
Abstracts/Lung
Cancer
An unusual case of a IO-year survival after removal of lung adenccarcinoma and brain metastasis is described and the pertinent literature is briefly reviewed. Although the prognosis ofpatients with lung tumors and brain metastases has significantly improved, cases with survival of more than 10 years remain rare. Patient candidates for long survivals are those with lung tumors different from the oat-cell carcinoma and with single supratentorial brain metastases, in whom complete removal of both primary and metastatic tumor is possible. In this selected group of patients an aggressive surgical treatment is justified.
Molecular and biological factors in the prognosis of non-small cell lung cancer Kanters SDJhI, Lammers SJ, Voest EE. Deportment Internal Medicine. University Hospital Utrecht. PO Box 85500. 3508 GA Utrecht. Eur Respir J 1995;8: 1389-97. For patients with non-small cell lung Caftcer the tumour/node/ metastasis (TNM) staging system and other conventional prognostic factors fail to predict the outcome oftreatment and survival accurately. New prognostic factors are urgently needed to improve understanding ofthe biologicalbebaviourofthediedifferentsubtypesofnon-small cell lungcancerandtorecognizepatients withagoodorpoorprognosis. This review will focus on molecular and biological factors published in the English language literature between 1988 and 1994. To be included in this survey, the predictive value ofa specific prognostic factor had to be contirmed by multivariate analysis in at least two different studies. Blood group antigen expression, ras oncogenes, microvessel density, and factors reflecting the proliferative state of the tumour may be important determinants of outcome of treatment. The search for new detemtinants of prognosis has provided insight in the complex tumour biology ofnon-small cell lung cancer and indicated possible targets for rumow therapy. Several promising prognostic factors have now been recognized. To validate these factors, prospective studies of a large patient population are needed. This ultimately serves the recognition of subsets of patients who may benefit from adjuvant therapy.
The peculiarities of metastatic spreading of lung cancer in cases of hereditary-related incidence ShutkinVA, WagnerRI, Barchuk AS. PetrovRes. InstituteofOncologv. Ministery of Health of Russian Fed.. St. Petersburg. Vopr Onkol 1994;40:25-9. Specific features of metastatic spreading of lung cancer have been compared in 258 surgical patients from families with a history of lung cancer incidence (group I) and in 861 controls (group II). Lesions in lymph nodes at various stages were more frequent in group I, metastatic spreading incidence increasing in step with stage. In is noteworthy that more frequent lesions in mediastinal lymph nodes (stage IV) were observed in group I (54.2%). as compared with 11.8% in controls (P
The effectiveness of transthoracic biopsy in diagnosis and treatment of neoplasms of chest organs Rodzaevsky SA, Babiy YaS. Yugrinov GG, Pozmogov AI, KIapchuk AG, Tuganova T.N et al. UT. Res. Inst. Oncol. andRadio1.. Ministry of Health of L&aine. Kiev. Vopr Onkol 1994;40:29-35. A complex examination of 1400 patients with pathologies of the lungsandmediastinum wascaniedoutusingroentgenologic,endoscopic, biopticsndcytoIogicmethods.DiagnosiswascontinnedmorphologicalIy
14 (19%)
149- I79
161
in 93.7% of cases. More specific information was obtained by express cytologic examination in 97.9% of cases of malignant growth and in 64.4% with benign tumors. On the basis ofthe test results, preoperative intratumor chemotherapy technique suggested by the authors may be recommended for clinical use.
p53 and disease progression in patients with non-small cell lung cancer Sauter ER. Gwin JL, Mandel J, Keller SM. Department ofSurgery, Beth Israel Medical Center. New York, NY 10029. Surg Oncol 1995;4: 15761. Present methods of predicting nodal progression preoperatively in patients with non-small cell hmg cancer (NSCLC) are inadequate. Our hypothesis was that ~53 expression in primary NSCLC would predict disease progression, making it a useful marker of adverse outcome. From 1987 to 1992,sixty-eight consecutive NSCLC patientsunderwent potentiallycurative lungresectionandmediastinal lymphnodedissection byonesurgeon.Primarytumoumwereanalysedusingthep53monoclonal antibody 180 1. p53 overexpression was found in 53% of tumours. ~53 expressiondidnot correlate withage,gender, histology or stage. A trend toward a higher incidence of ~53 expression was seen in tumours with nodal spread (P = 0.06), and ~53 expression correlated significantly (P = 0.03) with improved disease-free survival in patients with squamous cell carcinoma (SCC). p53 was the fourth most important independent predictor of survival, behind histology, gender and nodal disease. As a weakindependentpredictorofsurvival, thecorrelationofp53 expression with survival in patients with SCC must be evaluated with caution. If borne out in a larger patient population, ~53 expression may be a marker of nodal disease progression in patients with NSCLC.
Prognostic significance ofCD44 expression in adenocarcinoma of the lung Clarke MR. Landreneau RI, Resnick NM, Crowley R. Dougherty GJ. Cooper DL et al. Department of Pathologv, (Jniversity Pittsburgh Sch. Medicine, ZOOLothropStreet. Pittsburgh, PA 15232-2582. JClin Path01 Clin Mol Path01 1995;48:M200-4. Aims - To determine whether expression of CD44 in neoplasia is associated with tumour grade, stage and prognosis. Methods - The immunohistochemical expression of CD44 was evaluated using the mouse antihuman monoclonal antibody 3G I2 which recognises regions shared by all CD44 isoforms to determine whether expression in formalin fixed, paraffin wax embedded tissue correlates with tumour grade, stage or survival in adenocarcinoma of the lung. Thirty one adenocarcinomas of the lung. 16 TZNO and I5 T2Nl . and their nodal metastases were studied. Results - Of the 3 1 tumours, 25 were positive for the CD44 antigen. CD44 expression correlated with tumour grade. in that intense staining was seen only in moderately and/or poorly differentiated tumours. CD44 did not correlate with nodal status. tumow size, pleural invasion, angiolymphatic invasion, or host inflammatory response, but did correlate with survival. A median survival of 46 monthswasobservedinpatientswithmoderatetostrongCD44expression compared with 24 months for those with no or weak expression. Nine patients were alive without evidence of disease at a median follow up of 61 months. Six (66%) of these nine patients had strong CD44 expression. This contrasts with strong expression in only three ( 17%) of the 17 patients dying with a median survival of 28 months. Conclusion - In primary adenocarcinoma of the lung loss of CD44 expression IS associated with less favorable outcome and may indicate a more aggressive neoplasm. CD44 may be a useful prognostic marker m lung carcinoma.
Cancer
An unusual case of a IO-year survival after removal of lung adenccarcinoma and brain metastasis is described and the pertinent literature is briefly reviewed. Although the prognosis ofpatients with lung tumors and brain metastases has significantly improved, cases with survival of more than 10 years remain rare. Patient candidates for long survivals are those with lung tumors different from the oat-cell carcinoma and with single supratentorial brain metastases, in whom complete removal of both primary and metastatic tumor is possible. In this selected group of patients an aggressive surgical treatment is justified.
Molecular and biological factors in the prognosis of non-small cell lung cancer Kanters SDJhI, Lammers SJ, Voest EE. Deportment Internal Medicine. University Hospital Utrecht. PO Box 85500. 3508 GA Utrecht. Eur Respir J 1995;8: 1389-97. For patients with non-small cell lung Caftcer the tumour/node/ metastasis (TNM) staging system and other conventional prognostic factors fail to predict the outcome oftreatment and survival accurately. New prognostic factors are urgently needed to improve understanding ofthe biologicalbebaviourofthediedifferentsubtypesofnon-small cell lungcancerandtorecognizepatients withagoodorpoorprognosis. This review will focus on molecular and biological factors published in the English language literature between 1988 and 1994. To be included in this survey, the predictive value ofa specific prognostic factor had to be contirmed by multivariate analysis in at least two different studies. Blood group antigen expression, ras oncogenes, microvessel density, and factors reflecting the proliferative state of the tumour may be important determinants of outcome of treatment. The search for new detemtinants of prognosis has provided insight in the complex tumour biology ofnon-small cell lung cancer and indicated possible targets for rumow therapy. Several promising prognostic factors have now been recognized. To validate these factors, prospective studies of a large patient population are needed. This ultimately serves the recognition of subsets of patients who may benefit from adjuvant therapy.
The peculiarities of metastatic spreading of lung cancer in cases of hereditary-related incidence ShutkinVA, WagnerRI, Barchuk AS. PetrovRes. InstituteofOncologv. Ministery of Health of Russian Fed.. St. Petersburg. Vopr Onkol 1994;40:25-9. Specific features of metastatic spreading of lung cancer have been compared in 258 surgical patients from families with a history of lung cancer incidence (group I) and in 861 controls (group II). Lesions in lymph nodes at various stages were more frequent in group I, metastatic spreading incidence increasing in step with stage. In is noteworthy that more frequent lesions in mediastinal lymph nodes (stage IV) were observed in group I (54.2%). as compared with 11.8% in controls (P
The effectiveness of transthoracic biopsy in diagnosis and treatment of neoplasms of chest organs Rodzaevsky SA, Babiy YaS. Yugrinov GG, Pozmogov AI, KIapchuk AG, Tuganova T.N et al. UT. Res. Inst. Oncol. andRadio1.. Ministry of Health of L&aine. Kiev. Vopr Onkol 1994;40:29-35. A complex examination of 1400 patients with pathologies of the lungsandmediastinum wascaniedoutusingroentgenologic,endoscopic, biopticsndcytoIogicmethods.DiagnosiswascontinnedmorphologicalIy
14 (19%)
149- I79
161
in 93.7% of cases. More specific information was obtained by express cytologic examination in 97.9% of cases of malignant growth and in 64.4% with benign tumors. On the basis ofthe test results, preoperative intratumor chemotherapy technique suggested by the authors may be recommended for clinical use.
p53 and disease progression in patients with non-small cell lung cancer Sauter ER. Gwin JL, Mandel J, Keller SM. Department ofSurgery, Beth Israel Medical Center. New York, NY 10029. Surg Oncol 1995;4: 15761. Present methods of predicting nodal progression preoperatively in patients with non-small cell hmg cancer (NSCLC) are inadequate. Our hypothesis was that ~53 expression in primary NSCLC would predict disease progression, making it a useful marker of adverse outcome. From 1987 to 1992,sixty-eight consecutive NSCLC patientsunderwent potentiallycurative lungresectionandmediastinal lymphnodedissection byonesurgeon.Primarytumoumwereanalysedusingthep53monoclonal antibody 180 1. p53 overexpression was found in 53% of tumours. ~53 expressiondidnot correlate withage,gender, histology or stage. A trend toward a higher incidence of ~53 expression was seen in tumours with nodal spread (P = 0.06), and ~53 expression correlated significantly (P = 0.03) with improved disease-free survival in patients with squamous cell carcinoma (SCC). p53 was the fourth most important independent predictor of survival, behind histology, gender and nodal disease. As a weakindependentpredictorofsurvival, thecorrelationofp53 expression with survival in patients with SCC must be evaluated with caution. If borne out in a larger patient population, ~53 expression may be a marker of nodal disease progression in patients with NSCLC.
Prognostic significance ofCD44 expression in adenocarcinoma of the lung Clarke MR. Landreneau RI, Resnick NM, Crowley R. Dougherty GJ. Cooper DL et al. Department of Pathologv, (Jniversity Pittsburgh Sch. Medicine, ZOOLothropStreet. Pittsburgh, PA 15232-2582. JClin Path01 Clin Mol Path01 1995;48:M200-4. Aims - To determine whether expression of CD44 in neoplasia is associated with tumour grade, stage and prognosis. Methods - The immunohistochemical expression of CD44 was evaluated using the mouse antihuman monoclonal antibody 3G I2 which recognises regions shared by all CD44 isoforms to determine whether expression in formalin fixed, paraffin wax embedded tissue correlates with tumour grade, stage or survival in adenocarcinoma of the lung. Thirty one adenocarcinomas of the lung. 16 TZNO and I5 T2Nl . and their nodal metastases were studied. Results - Of the 3 1 tumours, 25 were positive for the CD44 antigen. CD44 expression correlated with tumour grade. in that intense staining was seen only in moderately and/or poorly differentiated tumours. CD44 did not correlate with nodal status. tumow size, pleural invasion, angiolymphatic invasion, or host inflammatory response, but did correlate with survival. A median survival of 46 monthswasobservedinpatientswithmoderatetostrongCD44expression compared with 24 months for those with no or weak expression. Nine patients were alive without evidence of disease at a median follow up of 61 months. Six (66%) of these nine patients had strong CD44 expression. This contrasts with strong expression in only three ( 17%) of the 17 patients dying with a median survival of 28 months. Conclusion - In primary adenocarcinoma of the lung loss of CD44 expression IS associated with less favorable outcome and may indicate a more aggressive neoplasm. CD44 may be a useful prognostic marker m lung carcinoma.