Expression Of TTF-1, CK7, CK20 In Bronchioloalveolar Carcinoma And Their Prognostic Implications

Objective: To study the clinic characteristics and prognostic factors ofbronchioloalveolar carcinoma (BAC). Furthermore, to evaluate the expression andclinical significance of thyroid transcription factor-1 (TTF-1) and cytokeratinsubtypes (CKT, CK20) in BAC, and investigate the value of these factors inidentification of the prognosis of BAC in order to provide evidence for clinicaltherapy.Method: Clinic data of 107 inpatient cases in The Cancer Hospital of TianjinMedical University, from 1990-2000, were retrospectively reviewed. Expression ofTTF-1, CK7 and CK20 of 81 cases that were surgically resected BAC specimens(including 68 nonmucinous types and 13 mucinous types) was studied byimmunohistochemistry. The value of the three factors in identification of theprognosis of BAC was examined by survival analysis.Result:1. Result of clinical dataThe overall 1, 3 and 5-year survival rates were 88.7, 64.8 and 48.6% respectively.The main prognostic factors were tumor diameter (P=0.022), bronchial stump(P=0.016), TNM stage (P=0.000), T stage (P=0.002), N stage (P=0.000) andpostoperation radiotherapy (P=0.001). Age (≥60 or＜60 years), gender, smoking,sputum cytology, pathology from bronchoscope, positive mediastinal lymph nodesfrom CT scans, pleural effusion, tumor location, surgical intervention, dissection oflymph nodes (≥6 or＜6), postoperative chemotherapy and biotherapy were notsignificant prognostic factors (P＞0.05). Cox regression analysis suggested that the TNM stage (P=0.000) and tumor diameter (P=0.015) are independent factorsaffecting the prognosis.2. The expression of TTF-1, CK7 and CK20 in BAC and their significancesThe positive rate of TTF-1 was significantly higher in stageⅢand nonmucinoustypes than that in stageⅠ-Ⅱand mucinous types (P＜0.05). No significant correlationwas found between CK7 positive rate and age-groups, clinical stages andpathological subtypes of BAC (P＞0.05). The positive rate of CK20 was higher instageⅠ-Ⅱand mucinous types than that in stageⅢand nonmucinous types. Therewas a statistically significant positive correlation between expression of CK7 andTTF-1 (r=0.257, P=0.021). Strata analysis suggested that the survival time of BACwith TTF-1 positive was superior to that with TTF-1negative in nonmucinous types(P=0.009), and the survival time of BAC with TTF-1 positive was superior to thatwith TTF-1 negative in stageⅢ(P=0.022). Cox Regression suggested that TTF-1,TNM stage, N stage and tumor diameter were independent factors affecting theprognosis of bronchioloalveolar carcinoma.Conclusion: BAC is an important subtype of pulmonary adenocarcinoma that hasa special biological behaviour, as well as a special clinical, radiological andpathological presentation. The overall survival rate of BAC patients was superior tothose with other non-small cell lung cancer (NSCLC). The expression of TTF-1,CK7 and CK20 has a higher specificity, and there is a statistically significant positivecorrelation between expression of CK7 and TTF-1. CK7(+)/CK20(-) immunoprofileis a valuable diagnostic marker for differentiating primary lung adenocarcinoma frommetastatic adenocarcinoma. TTF-1 and CK20 provide a new evidence for themolecular staging of BAC. TTF-1, TNM stage, tumor diameter and N stage are allindependent factors affecting the prognosis of BAC.