Isabel Rodrigo

bcl-2 Expression and Apoptosis in Primary and Metastatic Breast Carcinomas

Objectives: To evaluate the role of bcl-2 and apoptotic index in the progression from primary to metastatic breast carcinoma and their influence on prognosis. Methods:bcl-2 expression was examined by immunohistochemistry and apoptotic index by in situ end-labelling in 116 surgical breast carcinomas and lymph node metastases from 50 patients. Results:bcl-2 was observed in 69 cases (59.4%) of primitive carcinomas and 26 cases (65%) of metastatic breast carcinomas and there was agreement of bcl-2 expression between primary and metastatic sites except in 3 cases. bcl-2 expression was significantly associated with several favourable prognostic features, such as small tumour size (p = 0.03) and oestrogen and progesterone-receptor positivity (p < 0.01 and p < 0.001, respectively). A high apoptotic index was significantly associated with a number of poor prognostic factors, including poorly differentiated carcinomas, large tumour size, high Ki67 expression and high mitotic count (p < 0.001 in all cases). The mean apoptotic index was higher in lymph node metastasis than in primary carcinomas (1.19 vs. 0.69, p < 0.01). A low bcl-2 expression and a high apoptotic index were significantly associated with short-relapse free survival rates (p = 0.02 and p < 0.01, respectively), but only apoptotic extent provided independent prognostic information by multivariate analysis. Conclusions: The evaluation of bcl-2 expression and extent of apoptosis may provide useful prognostic information on breast cancer patients; however while increased apoptosis is strongly associated with the progression from primary carcinomas to lymph node metastases, bcl-2 does not seem to play a significant role in this process.

Clusterin expression is associated with decreased disease‐free survival of patients with colorectal carcinomas

Redondo M, Rodrigo I, Alcaide J, Tellez T, Roldan M J, Funez R, Diaz‐Martin A, Rueda A & Jiménez E
(2010) Histopathology 56, 932–936
Clusterin expression is associated with decreased disease‐free survival of patients with colorectal carcinomas

Prognostic implications of emergency admission and delays in patients with breast cancer

IntroductionThis study evaluates clinical–pathological characteristics and survival rates associated with emergency admission and delays in diagnosis and treatment of 411 consecutive breast cancer patients.Materials and methodsEmergency admission and first symptom–first hospital visit delay were significantly associated with advanced tumor stages but only in the former case with short disease-free survival (RR 2.5, CI 95% 1.5–4.2).ResultsBrief diagnostic delays were significantly associated with advanced disease stage and poor survival rates (RR 2.04; CI 95% 1.08–3.82) probably because sicker patients receive prompt medical attention.

Detection methods predict differences in biology and survival in breast cancer patients

BackgroundThe aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences.MethodsFor this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors.ResultsAfter adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19).ConclusionsIncident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions.

Expression of bax and p53 Proteins in the Tumorigenesis and Progression of Breast Carcinomas

Objectives: Dysregulation of normal programmed cell death mechanisms plays an important role in the pathogenesis of breast cancer. The purpose of this study was to investigate the role of bax and p53 expression in tumorigenesis and progression of breast carcinoma as well as their relationship with proliferative and apoptotic activity. Methods: We used immunohistochemical methods and in situ detection of apoptotic cells to examine 30 carcinomas in situ (CIS), 131 invasive breast carcinomas and 45 lymph node metastases. Results: In 25% (33 of 131) of invasive breast carcinomas examined, bax expression was absent, while p53 accumulation was present in 37% (49 of 131). Interestingly, p53 accumulation and loss of bax expression occur in breast CIS as frequently as in invasive breast carcinoma. Thus, in 17% (5 of 30) of CIS bax expression was absent, and 30% (9 of 30) presented nuclear expression of p53. p53 accumulation was related to apoptosis and proliferative activity. However, the protein level of bax was unrelated to all parameters studied, including proliferation and apoptosis of tumor cells. A multivariate analysis of disease-free survival demonstrated that p53 accumulation and bax expression are not significant independent indicators of prognosis in operable breast carcinoma. Our results also show that the proportion of bax- and p53-positive cells does not vary between primary and metastatic tumors. Conclusions: p53 accumulation and loss of bax expression influence the acquisition of a malignant phenotype but seem to have no further impact on tumor progression.

The role and prognostic value of apoptosis in colorectal carcinoma

BackgroundAlterations to apoptosis are a common occurrence in human tumours. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of colorectal carcinomas (CRCs).MethodsA TUNEL assay was performed on archival material from 103 colorectal carcinomas, 26 adenomas and 20 samples of normal epithelia.ResultsThe number of apoptotic cells was higher in CRCs (1.09 ± 0.13) than in adenomas (0.38 ± 0.23, p = 0.059) and normal epithelium (0.06 ± 0.04, p = 0.001). In addition, the apoptotic index (AI) was greater in metastatic disease (stage IV) than in other stages (p = 0.017). No relationship was found between apoptotic rates and age, gender or tumour grade. However, patients with tumours that showed higher AI values had a significantly lower disease-free survival (DFS) and overall survival (OS) than those with tumours that had lower AIs (p = 0.020 and p = 0.027). In a multivariate Cox proportional hazards model, AI remained a significant independent predictor of survival.ConclusionsWe conclude that disregulated apoptosis is an important event during CRC development and progression. Higher AIs are associated with more aggressive tumours and a poorer prognosis for patients with CRC.

High serum vascular endothelial growth factor C predicts better relapse-free survival in early clinically node-negative breast cancer

A recent meta-analysis indicated that higher tumoral expression of vascular endothelial growth factor C (VEGF-C) was related to poorer relapse-free and overall survival in breast cancer patients. However, a retrospective study found that higher circulating VEGF-C levels were associated with better survival in breast cancer patients. In 2009, we initiated a prospective study to determine the utility of preoperative serum VEGF-C levels for predicting the risk of sentinel lymph node involvement in early breast cancer and to assess serum VEGF-C levels as a prognostic factor for relapse-free and overall survival. We analyzed serum samples from 174 patients with early breast cancer who underwent sentinel lymph node biopsies. VEGF-C levels were determined using an ELISA. Serum VEGF-C levels were normally distributed, with a median value of 6561.5 pg/mL, and did not correlate with any other clinical or pathological variables. During a median follow-up period of 58 months, the five-year relapse-free survival rate was higher in patients with VEGF-C levels above the median than in patients with lower levels (95.3% vs. 85.9%, p < 0.04). No association was found between VEGF-C levels and overall survival. Our study demonstrates that the prognosis was better for early breast cancer patients with high serum VEGF-C levels.

Clusterin expression (CLU) as a prognostic marker in colorectal carcinoma (CCR).

563 Background: Increased CLU is involved in malignant progression and anticlusterin treatment with antisense oligonucleotides enhances apoptosis induced by several citotoxics. However, clinical significance of CLU expression in human CRCs has been scarcely studied. We investigated whether changes in CLU could be related to carcinogenesis and survival (sv) of CRC patients (pts). Methods: Formalin-fixed and paraffin-embedded specimens were examined from 31 adenomas and 103 CRCs resected at Costa del Sol Hospital. The study was approved by Research Ethics Committee. Immunohistochemistry using monoclonal anti-α chain clusterin antibody (Upstate-Millipore, Watford, England) was performed, following standard staining procedure. CLU was scored as negative (CLU–) (no staining) or positive (CLU +) (>10% of tumor cells with strong staining). Cytoplasmic CLU in tumors was evaluated for cancer cells only, and in normal mucosa for epithelial cells only. Sv curves were calculated and plotted according to Kaplan-Meier ...