Clinical value of p53, c‐erbB‐2, CEA and CA125 regarding relapse, metastasis and death in resectable non‐small cell lung cancer

Abstract

The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), locoregional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lungcancer recurrence. They can add useful information regarding the complex nature of prognosis. Prognosis for non-small cell lung cancer (NSCLC) has remained disappointing over the last decades, even in localized stages that are amenable to curative surgery. 1 Recurrence rates among patients with resectable NSCLC are substantial, 2-4 and only around 50% of them will be alive after 5 years. 5 The clinical or pathologic TNM staging (T, primary tumor; N, regional lymph nodes; M, distant metastasis) does not always provide a satisfactory explanation for differences in relapse and survival. It is of major importance, however, to be able to anticipate a bad prognosis to prescribe an active chemotherapy or radiotherapy adjuvant program. 6,7 In this context, a large number of articles have been published proposing the incorporation of different prognostic markers in clinical practice, 8 but the interpretation and integration of their results is hampered by methodological problems. Many studies included a low number of patients, and very few examined more than 1 or 2 markers. Furthermore, the majority are retrospective cohorts, where the quality of the follow-up is uncertain and the possibility of a selection bias cannot be ruled out. 9 Prognostic studies try to identify one or more variables that might be useful to classify a heterogeneous population into smaller subgroups with more predictable outcomes. This classification will serve to apply therapy more efficiently, avoiding...

Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression

“…Elevated CA125 levels have been associated with various non-malignant conditions, including pregnancy, endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease, menstruation and benign ovarian cysts (8). Furthermore, abnormal CA125 levels have been associated with other malignancies, including pancreatic (9), breast (10), lung (11), gastric (12) and colorectal cancer (13), particularly when they are associated with peritoneal spreading. CA125 may not be useful in identifying early stages or providing a differential diagnosis for these diseases, as malignancies with peritoneal spreading typically exhibit a high level of CA125.…”

Reduced FEZ1/LZTS1 Expression and Outcome Prediction in Lung Cancer

“…Although the low study power doesn't allow drawing firm conclusions it is possible therefore that lack of Fez1 expression might turn out to be a negative prognostic factor in lung cancer. This is a promising observation because although many markers, including p53, bcl-2, Rb, K-ras, and c-erbB-2 have been investigated as predictors of outcome in lung cancer (30)(31)(32), their clinical significance is often controversial (33), and a definitive role seems firmly established only for few of them (e.g., p53 mutations in stage I NSCLC; ref. 34).…”

Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling

“…The extracellular domain encompasses an interactive disulfide bridged cysteine-loop and the site of OC125 and M11 binding (O’Brien et al 2001). It is known to be a marker in several cancers, including ovarian (Yin et al 2002), renal (Bamias et al 2003), and lung (Pollan et al 2003). …”