Summary Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A. The analysis was intended to determine whether cyclin A has additional prognostic value for predicting patients' survival and drug response. Estimating the proliferative activity of tumours is important for the management and prognosis of tumour patients. Using flow cytometry in an earlier study, we found that patients with non-small-cell lung carcinomas (NSCLC) who had tumours with a high proliferative activity (high proportion of S and G2/M cells) had significantly shorter survival times than patients with tumours having a low proliferative activity (Volm et al, 1985(Volm et al, , 1988. Patients with ovarian carcinomas having high proliferative activity also died earlier than patients with carcinomas having low proliferative activity (Volm et al, 1985). However, there were various limitations in the earlier assays. A disadvantage of flow cytometry was that such analyses required fresh tissues and single-cell suspensions. In our earlier studies, cell cycle analyses were also not possible in all tumour samples because DNA stemlines overlapped. In contrast, immunohistochemical analysis applies to small tumour specimens and to archival material.Cell cycle progression is controlled by protein complexes composed of cyclins and cyclin-dependent kinases (Cdks); the cyclins act as regulatory molecules and the Cdks as catalytic subunits (Cordon-Cardo, 1995). The periodic appearance of the different cyclins in distinct phases of the cell cycle suggests that these proteins can also be used as markers for tissue proliferation (Dutta et al, 1995).In the present investigation, we analysed formalin-fixed, paraffin-embedded tumour sections from patients with NSCLC for expression of cyclin A. Using immunohistochemistry, we determined the relevance of cyclin A for patient survival and drug response in vitro. MATERIALS AND METHODS Patients and tumoursOne hundred and eighty-seven patients with previously untreated non-small-cell lung carcinomas (NSCLC) were admitted into this study. All patients were surgically treated in the Chest Hospital Heidelberg-Rohrbach. The minimum follow-up time is 5 years. The morphological classification of the carcinomas was conducted according to the WHO study (1981). Tumour classifications were carried out by two pathologists. Of the 187 tumours, 107 were epidermoid carcinomas, 50 adenocarcinomas and 30 large-cell carcinomas. All patients were staged at the time of their surgery according to the guidelines of the American Joint Committee on Cancer (Carr and Mountain, 1977). Thirty-seven patients had stage I, 17 had stage II and 133 had stage III tumours. The patients (167 men, 20 women) ranged in age from 28 to 76 years (average age 58 years). Seventy-one patients did not have lymph node involvement, while 115 patients had lymph node involvement (one patient could not be classified). One hundred and twenty-seven patients were treated ...

Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias (ALL) for their expression of cyclins (D1, E, A), cyclin‐dependent kinases (cdk2, cdk4) and tumor‐suppressor genes (pRb, p16INK4A), in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL. Patients with ALL who were strongly positive for cyclin D1 had a lower probability of remaining in first continuous remission than ALL patients who were negative or weakly positive for this trait. There was also a significant correlation between expression of cyclin D1 and frequency of recurrence. For cyclin E and cyclin A, in contrast, there was no difference in the duration of relapse‐free‐intervals or the frequency of recurrence in patients. Children with cdk4‐positive ALL had a lower probability of remaining in first continuous remission than children with cdk4‐negative ALL. No prognostic relevance was found for cdk2. Patients with ALL who expressed pRb had a higher probability and patients who expressed p16 a lower probability of remaining in first continuous remission, but the results were not statistically significant. This investigation demonstrated that cyclin D1 and cdk4 were the most important prognostic factors for children with ALL, and that the combination of them showed the strongest prognostic relevance. Int. J. Cancer 74:508–512, 1997. © 1997 Wiley‐Liss, Inc.

Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias (ALL) for their expression of cyclins (D1, E, A), cyclindependent kinases (cdk2, cdk4) and tumor-suppressor genes (pRb, p16 INK4A ), in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL. Patients with ALL who were strongly positive for cyclin D1 had a lower probability of remaining in first continuous remission than ALL patients who were negative or weakly positive for this trait. There was also a significant correlation between expression of cyclin D1 and frequency of recurrence. For cyclin E and cyclin A, in contrast, there was no difference in the duration of relapse-free-intervals or the frequency of recurrence in patients. Children with cdk4-positive ALL had a lower probability of remaining in first continuous remission than children with cdk4-negative ALL. No prognostic relevance was found for cdk2. Patients with ALL who expressed pRb had a higher probability and patients who expressed p16 a lower probability of remaining in first continuous remission, but the results were not statistically significant. This investigation demonstrated that cyclin D1 and cdk4 were the most important prognostic factors for children with ALL, and that the combination of them showed the strongest prognostic relevance.

No abstract