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Giuseppe Viale

Publications and source records attributed to Giuseppe Viale.

101 records · Page 6Linked to original sources

p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas?

The p63 protein, a member of the p53 family of nuclear transcription factors, is characterized by different capabilities of transactivating reporter genes, inducing apoptosis, and functioning as dominant-negative agent. This study evaluated the prevalence and prognostic implications of p63 immunoreactivity in 221 patients with stage I non-small cell lung carcinoma (NSCLC) and in 57 patients with stage I-IV neuroendocrine tumours (NET). The results were correlated with the tumour proliferative fraction, the accumulation of p53 protein, and with patient survival. p63 immunoreactivity was seen in 109/118 squamous cell carcinomas, 15/95 adenocarcinomas, 2/2 adenosquamous carcinomas, 4/6 large cell carcinomas, 9/20 poorly differentiated NET, and 1/37 typical and atypical carcinoids (p < 0.001). Furthermore, the prevalence of p63-immunoreactive cells increased progressively from pre-neoplastic and pre-invasive lesions to invasive squamous cell carcinomas. In these latter tumours, but not in adenocarcinomas, p63 immunoreactivity correlated directly with the tumour proliferative fraction (p = 0.028), and inversely with the tumour grade (p = 0.004). No relationship was found with p53 protein immunoreactivity or the other clinico-pathological variables examined. Although p63 is likely to be involved in the development of pulmonary squamous cell carcinoma, it does not carry any prognostic implication for NSCLC patients.

Adenocarcinoma↗

Pathologic and biological prognostic factors of breast cancers in short- and long-term hormone replacement therapy users.

BACKGROUND: Breast cancer tumors occurring in hormone replacement therapy (HRT) users are less aggressive, but no studies have compared tumor aggressiveness among HRT users by length and mode of therapy. METHODS: A total of 1105 consecutive postmenopausal patients treated for operable breast cancer at the European Institute of Oncology were identified. Women exposed to HRT were compared with HRT nonusers by clinical stage at presentation and pathologic and biological tumor characteristics. HRT duration and administration modality were analyzed in relation to tumor characteristics in the HRT group. RESULTS: Better stage distribution, including smaller pathologic tumor diameter and fewer involved axillary lymph nodes, was seen in the HRT group. Estrogen receptor-positive tumors were more frequent in the control group, but this tendency was reversed with longer exposure to HRT. Histological grade III tumors were less frequent in the HRT group. More favorable prognostic factors were associated with HRT >5 years. The proliferative fraction was higher in patients with exposure <1 vs. >5 years and in oral versus transdermal users. CONCLUSIONS: Breast cancers developing during HRT have better prognostic characteristics than those seen in HRT nonusers. A trend toward better prognostic characteristics with increasing duration of HRT was seen.

Aged↗

Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients.

We evaluated microvessel density (MVD) in bone marrow biopsies (BM) from multiple myeloma (MM) patients after staining with anti-CD34 and anti-CD105 antibodies (mAbs). The anti-CD105 mAb was significantly more sensitive than the anti-CD34 mAb in visualizing blood vessels both in controls and MM samples. MVD was significantly higher in MM than in controls with both anti-CD34 and anti-CD105 mAbs. Patients with low CD34+ MVD survived longer than patients with higher MVD (P = 0.01), whereas there was no difference in survival between patients with low and high CD105+ MVD. Multivariate analysis confirmed the independent significant association between CD34+ MVD and survival (P = 0.001).

Adult↗

p63 in laryngeal squamous cell carcinoma: evidence for a role of TA-p63 down-regulation in tumorigenesis and lack of prognostic implications of p63 immunoreactivity.

p63 is a p53-related gene that encodes for multiple mRNA transcripts with (TA-p63) or without (DeltaN-p63) transactivating properties on p53-responsive genes. We evaluated for the first time the prevalence and clinical implications of p63 immunoreactivity (IR) and mRNA expression in laryngeal squamous cell carcinomas (LSCCs). Moreover, we also assessed the relationships between p63 expression and p53 gene status. p63 IR was detectable in the basal cell layers of non-neoplastic epithelium and in the whole thickness of dysplastic epithelium. All the 150 LSCCs analyzed were immunoreactive for p63, with 28 (18.7%) cases showing p63 IR in </=50% of neoplastic cells. DeltaN-p63 mRNA transcripts were detected in all the 23 tumors analyzed, whereas TA-p63 mRNA transcripts were absent in 5 (21.7%) cases. p53 gene mutations were found in 24 (29.2%) of the 82 cases analyzed and p53 IR was found in 58 (53.7%) of the 108 cases analyzed; neither was associated with p63 IR. No significant association was found between p63 IR and patients' survival. Interestingly, down-regulation of TA-p63 mRNA levels was more prevalent in patients with T3-T4 tumors and advanced clinical stage. Although the risk of death for cancer was higher in these patients (40% versus 16.6%), this difference did not reach statistical significance. Our results suggest that abnormal expression of p63 may be involved in the early phases of laryngeal tumorigenesis irrespective of p53 gene status and that TA-p63 mRNA down-regulation, but not p63 IR, may be clinically relevant in patients with LSCC.

Adult↗

Breast cancer.

Breast cancer remains a public-health issue on a global scale. We report new information about the disease from the past 5 years. Early age at first birth, increasing parity, and tamoxifen use are related to long-term lifetime reduction in breast-cancer risk. Ductal carcinomas in situ has been suggested to be renamed ductal intraepithelial neoplasia to emphasise its non-life-threatening nature. An alternative approach, the progenitor/stem cell theory, predicts that only some tumour cells cause cancer progression and that these should be targeted by treatment. Mammography and ultrasonography are still the most effective for women with non-dense and dense breast tissues, respectively. Additionally, MRI, lymphatic mapping, the nipple-sparing mastectomy, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant treatments are promising for subgroups of breast-cancer patients. Although tamoxifen can be offered for endocrine-responsive disease, aromatase inhibitors are increasingly used. Assessment of potential molecular targets is now important in primary diagnosis. Tyrosine-kinase inhibitors and other drugs with anti-angiogenesis properties are currently undergoing preclinical investigations.

Breast Neoplasms↗

Adenomyoepithelioma of the breast, presenting as a cancer.

AIMS AND BACKGROUND: Adenomyoepithelioma is a rare lesion that can involve the breast tissue. The diagnostic appearance of the lesion can give rise to a difficult differential diagnosis with breast carcinoma. PATIENTS AND METHODS: We report our experience with a case of adenomyoepithelioma whose differential diagnosis with a breast carcinoma was particularly difficult, leading to surgery for definitive histology. DISCUSSION: Few papers are available with evidence about adenomyoepithelioma. The difficult differential diagnosis and the potentiality of malignant evolution of this lesion could in principle justify a conservative surgical approach for final histology.

Adenomyoma↗

Clinical application of spectral electromagnetic interaction in breast cancer: diagnostic results of a pilot study.

AIMS AND BACKGROUND: There is a need for a cost-effective method to safely reduce the number of diagnostic procedures women undergo for breast cancer. We tested a new procedure for breast cancer diagnosis based on breast tissue response to low level electromagnetic incident waves. METHODS: We tested 101 patients with suspicious palpable breast lesions detected by mammography or ultrasonography, who were scheduled to undergo an open biopsy. Using an electromagnetic field generator (tissue resonance interaction method probe [TRIMprob]), we passed the TRIMprob over the breast area and recorded the signal variation of one or more spectral lines (dB1, dB2, dB3). The results were compared with those of a control group as well as with pathology data obtained from excisional biopsy. RESULTS: No adverse effects of the test were observed. Pathology revealed 86 malignant breast cancers (72 invasive, 14 in situ) and 15 benign conditions. We achieved the best discrimination between normal breasts and lesions using dB1 (dB1 AUC-ROC = 0.8; dB2 AUC-ROC = 0.61; dB3 AUC-ROC = 0.76). With a specificity of 75% to 95%, the sensitivity ranged from 49% to 84%. Tumor or patient variables did not influence the results. CONCLUSIONS: The TRIMprob test was able to provide some degree of discrimination between normal breast tissue and lesions but not between benign and malignant lesions. The lack of influence of patient age and tumor size on test results might be advantageous in terms of early diagnosis in young women. These preliminary results need to be verified and extended in a preclinical-stage disease setting before clinical applicability can be envisaged.

Adult↗

Serum levels of HER2 ECD can determine the response rate to low dose oral cyclophosphamide and methotrexate in patients with advanced stage breast carcinoma.

BACKGROUND: The proto-oncogene HER2/neu encodes for a transmembrane receptor protein whose overexpression in breast cancer may be associated with poor prognosis. Its extracellular domain (HER2 ECD) can be shed into the circulation. The purpose of this study was to evaluate the predictive value of HER2 ECD in patients with advanced breast cancer. PATIENTS AND METHODS: HER2 ECD was determined in 39 patients with advanced breast cancer, treated with oral cyclophosphamide and methotrexate (CM) at low doses. HER2 ECD levels were determined with the Bayer Immuno 1 HER2/neu assay before and after 2 months of chemotherapy, when all the patients were re-evaluated. RESULTS: Based on the response to chemotherapy, the patients were divided into two groups: progressive disease (PD, 14 patients) and patients with clinical benefit (CB; i.e. patients with stable or responsive disease, 25 patients). The patients with PD had a mean baseline value of HER2 ECD of 38.3+/-69.2 ng/ml, while the group of CB showed lower levels (9.2+/-2.3 ng/ml, p<0.05). After 2 months, the mean value of HER2 ECD in the PD group increased to 71.6+/-146 ng/ml, while in the other group the levels did not change (9.7+/-2.4 ng/ml). At follow-up, significant differences were noted in both the time to progression and overall survival, with patients with increased levels of HER2 ECD at baseline (> or = 15 ng/ml) showing a worse clinical outcome. CONCLUSION: Increased pretreatment levels of HER2 ECD identify a subset of patients with more aggressive tumors and less response to CM chemotherapy. During therapy, increasing levels of HER2 ECD are associated with disease progression.

Administration, Oral↗

Surgical treatment of advanced colorectal cancer in the elderly.

The aim of the study was to compare the short and long-term outcomes of older and younger colorectal cancer patients with advanced disease resected with a curative intent. Six hundred and ninety-two patients were analysed. Four hundred and seventy-nine patients were younger than 70 years (Group 1), and 213 were 70 years of age or above (Group 2). The overall perioperative mortality rate in the younger group was 0.8% (n = 7), as against 1.4% (n = 3) in the elderly group (p = NS). The morbidity rates were 35% and 42%, respectively (p = NS). At univariate analysis, the elderly patients had a worse overall survival compared to the younger group, when only patients undergoing postoperative chemo-radiotherapy were considered (54% vs 67% overall survival at 5 years; p = 0.03). Using logistic regression analysis, tumour stage (p < 0.0001) and radicality of surgery (p < 0.0001) correlated significantly with overall survival rates in the elderly. Colorectal surgery for malignancy can be performed safely in the elderly with acceptable morbidity and mortality rates and long-term survival.

Age Factors↗