Cyclin A is associated with an unfavourable outcome in patients with non-small-cell lung carcinomas

Abstract

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 ...

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

“…We are aware of no clinical data on cyclin A as a predictive factor for chemotherapy in breast cancer. A preclinical study by Volm showed that breast cancer cell lines with high cyclin A were significantly more sensitive to doxorubicin than cell lines with low cyclin A activity (Volm et al, 1997). TFR: time to first relapse, TTPa: time to progression after anthracycline therapy, OSa: overall survival after anthracycline therapy, TTPdoc: time to progression after docetaxel therapy, OSdg: overall survival from diagnosis, OSdoc: overall survival after docetaxel therapy, MF: methotrexate fluorouracil, TTPmf: time to progression after methotrexate fluorouracil therapy, OSmf: overall survival after methotrexate fluorouracil therapy.…”

Prognostic significance of cyclin A in gastric cancer

“…Kawashima et al reported that cytotoxicity of 5-FU in human cancer cell lines correlates with cyclin A. 39 In nonsmall-cell lung carcinomas, expression of cyclin A correlates with response of doxorubicin in vitro, 40 and patients with soft tissue sarcoma 41 or head and neck squamous cell carcinoma 42 expressing high levels of cyclin A show a better response to chemotherapy. These data suggest that cyclin A overexpression may prove useful in selecting those gastric cancer patients who may benefit from chemotherapy.…”

A high proliferation rate measured by cyclin A predicts a favourable chemotherapy response in soft tissue sarcoma patients

“…There are very few reports on cyclin A as a marker of proliferative cell fraction in cancer. In two recent studies by Volm, tumour tissue negativity for cyclin A expression predicted a favourable outcome in non-small-cell lung cancer patients (Volm et al, 1997(Volm et al, , 1998. We are aware of no previous studies correlating cyclin A score of the tumour to chemotherapy response.…”