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Background. Preoperative plasma prolactin and carcinoembryonic antigen (CEA) levels were assessed to monitor disease recurrence and to identify low-risk and high-risk patients with Dukes B or C colorectal cancer. Methods. Prolactin and CEA were estimated by radioimmunoassay method. Blood samples were collected preoperatively and sequentially thereafter from patients with colorectal cancer (N = 114); the samples were compared with samples from age-matched healthy control subjects (smokers and nonsmokers, N = 45). For rest of the analysis, patients with Dukes A disease (N = 7) were not included because of the small number. In monitoring recurrences, the criteria for positive test for the two markers was a continual increase in the marker level after an initial decrease or persistent high level of the marker. These were the indicators of relapse or no response to treatment. To determine the efficacy of the preoperative markers, the patients were grouped according to disease status at the end of 3 years, i.e., patients who had response to the treatment modalities (N = 52) and patients who later had progressive disease (N = 55). To determine the prognostic significance of preoperative marker levels, the patients were divided according to the cutoff levels (upper normal limits); for prolactin the cutoff level was 20.0 ng/ml plasma, and for CEA it was 5.0 ng/ml plasma. Results. Both of the markers were significantly high in patients with colorectal cancer compared with the markers of their respective control subjects (P < 0.0001). In monitoring disease course, the predictive power of prolactin was 100%, whereas that of CEA was 66%. Prolactin showed a lead time of 2-3 months. Preoperative prolactin levels were significantly higher in patients who later had progressive disease (P < 0.001) than in patients who had response to the treatments. However, such an intergroup variation was not observed for CEA. Patients with preoperative levels of prolactin greater than 20.0 ng/ml had shorter overall survival times than did those with prolactin levels less than 20.0 ng/ml plasma; such a trend was not observed for patients with CEA levels less than 5.0 ng/ml and those with CEA levels greater than 5.0 ng/ml plasma. Conclusion. Prolactin is a better overall marker than is CEA in patients with Dukes B or C colorectal cancer. The authors recommend the use of plasma prolactin levels to help identify low-risk and high-risk patient subgroups so that high-risk patients may be followed up more intensely and treated accordingly. Hyperprolactinemic patients with Dukes B or C disease have shortened survival time.

The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I–III colon cancer.

Introduction: 5-flourouracil (5-FU) is one of the standard chemotherapeutic drugs used today in the treatment of colorectal cancer patients. Disruption of 5-FU metabolic pathway may contribute to altered effectiveness towards 5-FU-based therapy. Hence, the study of 5-FU metabolizing enzymes might have the potential efficacy to predict survival and response to treatment in colorectal cancer patients.Materials and methods: Immunohistochemical localization of 5-FU metabolic enzymes (TS, MTHFR, DPYD, and TP) was evaluated in 143 untreated patients with colorectal cancer; their prognostic and predictive values were also evaluated.Results: Immuno-positivity for TS, MTHFR, DPYD, and TP was observed in 77%, 75%, 88%, and 96% of colorectal cancer patients, respectively. Univariate survival analysis in total patients showed that low DPYD expression significantly predicted adverse overall survival (P=0.042). Moreover, subgroup of colon cancer patients with low TS expression was associated with unfavorable prognosis. TP expression also emerged as a prognosticator in the subgroup of early and advanced stage patients. Additionally, when effect of co-expression of 5-FU metabolic enzymes was evaluated in total patients, low coexpression of all four proteins was predictive of poor overall survival than for individuals expressing high coexpression of these proteins (P=0.045). In contrast, none of the 5-FU metabolic enzymes—either singly or on coexpression—emerged as a useful biomarker of potential therapeutic value when evaluated in the subgroup of patients treated with 5-FU alone or 5-FU plus oxaliplatin.Conclusion: The above findings suggest that coexpression of 5-FU metabolic enzymes possess significant prognostic value and could be useful biomarkers in colorectal cancer patients.

Aims and background In India, breast cancer is becoming the number one cancer in females. CD44 is believed to play a critical role in the metastatic process, and its spliced forms, especially CD44v6, bestow a metastatic phenotype onto non-metastatic cells. However, the biological significance of CD44v6 in tumor progression remains controversial. Hence, pursuing our interest based on previous observations of a significant association of CD44 standard with advanced stage and poor survival, the present study investigated CD44v6 expression in our series of breast cancer.Methods and study design For this purpose, 85 untreated primary breast cancer patients were enrolled. CD44v6 was localized immunohistochemically, and its mRNA transcript along with CD44v9 and CD44v10 mRNA were studied by reverse transcriptase polymerase chain reaction.Results Membranous and/or cytoplasmic staining of CD44v6 was observed in 48% of the primary breast cancers. CD44v6 protein expression showed no significant association with clinical risk factors and survival. At the RNA level, the expression of CD44v6, CD44v9 and CD44v10 in breast cancers was 44%, 22% and 36%, respectively. CD44v6 mRNA expression significantly correlated with CD44v9 (P = 0.013) and CD44v10 (P = 0.0001) but showed no correlation with its protein expression. Furthermore, except for CD44v6 mRNA, none of the other isoforms were associated with clinical risk factors or survival. Loss of CD44v6 mRNA was significantly associated with poor overall survival (P = 0.018). In multivariate overall survival analysis, loss of CD44v6 mRNA expression was a significant independent factor of a poor prognosis (P = 0.045) with a relative risk of 2.10, entering the equation at step three after stage and lymph node status.Conclusions Preliminary results suggest an important role of CD44v6 in our series of patients. Down-expression of CD44v6 may be associated with the tumor cell phenotype, facilitating aggressive growth properties that affect the prognosis. Free full text available at www.tumorionline.it

The present study evaluated 5 of the 8 main TP53 mutation hot spots in cancer by restriction site mutation analysis and compared the results with p53 protein expression in patients with cancer of the tongue. Tumor samples from 49 patients with tongue cancer were screened for TP53 mutations in exons 5 through 8 by PCR restriction site mutation analysis and for p53 protein expression by immunohistochemistry using the DO-7 antibody. Nuclear accumulation of p53 protein was seen in 22% (11/49) of the tumors, whereas none of the patients exhibited TP53 mutations in exons 5 through 8. The observed data suggest that TP53 mutations alone are not responsible for abnormal accumulation of p53 protein in tobacco-chewing-mediated tongue carcinogenesis.

Background The transition from epithelial keratin to mesenchymal vimentin expression marks an important step in the malignant progression of breast cancer. This study analyzed the clinical significance of cytokeratin and vimentin in patients with breast cancer.Materials and methods Expression of cytokeratin and vimentin was evaluated by immunohistochemistry on paraffin-embedded tissue sections of patients with breast cancer.Results Loss of cytokeratin was seen in 11% of the patients. A clearer trend towards loss of cytokeratin was observed in patients with stage IV disease and PR negativity. Weak cytokeratin expression was present in patients who developed recurrence or metastatic disease. Loss of cytokeratin was associated with reduced overall survival in univariate and multi-variate analysis, gain of vimentin expression was seen in 57% of breast carcinoma patients. It was higher in patients with lymph node positivity, advanced stage, HER2 positivity, and disease recurrence or metastasis. Multivariate survival analysis indicated that gain of vimentin expression was associated with reduced relapse-free survival.Conclusion Loss of cytokeratin and gain of vimentin expression are indicators of biologically aggressive breast carcinoma.

The purpose of this study was to assess the role of prolactin (PRL) in men with locally advanced tongue cancer. Circulating PRL was assayed immunoradiometrically in pretherapeutic and sequential blood samples of 99 patients with locally advanced tongue cancer. Patients were followed for 3 years or until their death within a stipulated time. Immunohistochemical localization of PRL was performed on formalin-fixed paraffin-embedded tissue sections. Tumoral prolactin receptors (PRLR) were estimated by ligand binding assay; the expression of PRL mRNA and PRLR mRNA were carried out by reverse transcriptase polymerase chain reaction (RT-PCR). Furthermore, PRL amplimer was sequenced and compared with human pituitary PRL amplimer. Pretherapeutic PRL levels were significantly higher in patients with locally advanced tongue cancer compared with controls (p = .01). Thirty-four percent (34 of 99) of the patients had hyperprolactinemia (PRL ≥15.0 ng/mL). Univariate survival analysis showed that patients with pretherapeutic hyperprolactinemia had a significantly shorter overall survival than patients with pretherapeutic PRL &lt;15.0 ng/mL serum (p = .0009). In multivariate analysis, PRL emerged as the most significant independent prognostic factor influencing overall survival. Furthermore, changes in serial PRL levels showed excellent correlation with response to therapy and progression of disease. Forty-four percent (24 of 54) of the tumors showed positive immunoreactivity with PRL antibody, indicating that PRL or a molecule similar to it is produced by tongue tumors. PRL mRNA expression was seen in 85% (43 of 50) of the tumors and confirmed the de novo synthesis of PRL. Sequence analysis of the 234 bp PRL amplimer revealed that the sequence was homologous to exon 5 of pituitary PRL mRNA. The action of PRL is mediated by PRLR, and it was observed that the PRLR positivity by ligand binding assay was 33%. The expression of PRLR mRNA by RT-PCR showed two forms of PRLR mRNA (ie, intermediate form [500–600 bp] seen in 82% (41 of 50 ) of the tumors and the long form [800–900 bp] seen in 36% (18 of 50) of the tumors. In 82% (41 of 50) of the tumors, either the intermediate or long form was seen. This multifaceted study of PRL suggests that tongue cancer cells produce PRL, and this ectopically produced PRL might be acting as a major local growth promoter by means of autocrine and paracrine mechanisms. Looking at its prognostic value and correlation with disease activity, it may provide new insights into treatment of tongue cancer. © 2000 John Wiley & Sons, Inc. Head Neck 22: 257–264, 2000.

The efficiency of the combination of two tumor-associated antigens in recognising head and neck cancer was evaluated. The markers studied were CEA and ferritin by radioimmunoassay. CEA was estimated in 22 controls and 41 head and neck cancer patients. There was no difference in CEA values of controls and head and neck cancer patients, suggesting that CEA was not specific for head and neck malignancies. We measured serum ferritin in 27 controls and 58 patients with head and neck cancer. The mean ferritin level was significantly higher in patients (P < 0.001) than in normal subjects. The ferritin level in patients with no evidence of clinical disease 8 months after treatment showed approximately normal levels, whereas the levels showed a tendency to increase or remain at high levels in patients with a poor prognosis, giving support to the contention that ferritin may prove to be a valuable adjunct in head and neck cancer.