Angiogenesis as a prognostic indicator in pancreatic ductal adenocarcinoma.

BACKGROUND: Angiogenesis has gained wide acceptance as a reliable prognostic factor in several solid tumors. However, to date, experience in pancreatic adenocarcinoma is limited. MATERIALS AND METHODS: Specimens from 45 patients radically operated on at our departments from 1988 to 1997 were stained immunohistochemically with the antibodies anti-mutant p53, anti-bcl2, anti Ki67 and anti-CD31. All the slides were reviewed by the same pathologist without knowledge of the patients' outcome. RESULTS: Mutant p53, Ki67 index and vessel count were significantly related to tumoral behaviour and patients' outcome. Among patients with nodal involvement (Stage III), cumulative survival between hypovascular and hypervascular subgroups differed significantly (p = 0.03). Angiogenesis was independent from TNM in assessing the patients'prognosis at COX analysis (p = 0.02). CONCLUSION: In patients with pancreatic adenocarcinoma, angiogenesis is a reliable indicator of tumor extension, lymph node status and survival. Its evaluation as a common procedure may contribute to a further improvement in the management of these patients and to a proper selection of those who could benefit from different follow-up protocols or adjuvant treatment.

Prognostic impact of CD31 antigen expression in anal canal carcinoma.

BACKGROUND/AIMS: CD31 is a platelet endothelial cell adhesion molecule. Thus CD31 immunostaining of vascular endothelial cells can be used to measure degree of angiogenesis. As angiogenesis is necessary for tumor growth and metastasis, microvessels density could be a predictor of prognosis. The purpose of this study was to examine the relationship between CD31 value and standard pathologic parameters and prognosis of anal canal carcinoma. METHODOLOGY: Twenty-four patients with anal canal carcinoma were evaluated. Five-micron sections of formalin-fixed, paraffin-embedded tissue were tested with monoclonal anti-CD31 antibody. CD31 value is considered positive if more than 185 vessels/mm2 were counted. Pearson's chi 2 test was employed to test for association between CD31 value and clinicopathological variables. RESULTS: We found no correlation between CD31 value and histologic type, lymph node involvement, patients age and neoplastic relapse. Significant correlation was found between CD31 score and depth of parietal invasion. CONCLUSIONS: The relapse type could strengthen the hypothesis that increased vascularity promotes neoplastic dissemination. As angiogenesis could be used as prognostic indicator to determine patients who may be at higher risk for relapse, our results warrant further confirmation. Development of markers of angiogenic activity in anal canal carcinoma must be an integral part of proper clinical trials.

nm23-H1 protein expression in anal canal carcinoma: does it correlate with prognosis?

BACKGROUND AND OBJECTIVES: Anatomic extent is not the sole axis of classification of tumors and of tumor patients relevant to treatment planning and estimation of prognosis. This results in the need to demonstrate an improvement in prognostic assessment and choice of therapy achieved by consideration of factors other than TNM. nm23 protein does prevent tumor from metastasizing and may also play a role in the control of growth and development. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma and to evaluate its influence on the outcome of patients after surgery or radiochemotherapy. METHODS: Twenty-two patients affected by anal canal carcinoma were evaluated. Each section was incubated with monoclonal antibody nm23 NDPK-A. Immunostaining was considered positive when at least 10% of the tumor cells were immunostained. RESULTS: nm23 immunoreactivity was detected in 6/22 (27.3%) tumors. No significant association was found between nm23 expression and prognosis. CONCLUSIONS: The mechanisms causing enhanced nm23-H1 expression in anal canal carcinoma are unknown. Although the level and expression were not correlated with prognosis, activation of nm23-H1 gene might be a prerequisite for oncogenesis in this type of tumor, while an alternate possibility is the modification of cellular characteristics in relation to proliferation and/or differentiation as a consequence of oncogenesis.

Clinical behavior of solitary fibrous tumors of the pleura. An immunohistochemical study.

Localized fibrous tumors of the pleura are uncommon, generally asymptomatic and usually have a benign behavior even if in a few cases a malignant variant can be observed. We report 11 cases of localized pleural neoplasms submitted to surgical resection during the period 1987-1996. The differentiation between the localized fibrous as well as the less frequent localized malignant mesothelioma has been researched employing cyto-histopathologic and immunohistochemical assays. For the purpose of identifying solitary fibrous tumors of pleura that will behave in malignant manner, we applied the more recent criteria of specific immunohistochemical stains, microvessel density and proliferation mdex. All solitary fibrous tumors resulted positive for Vimentin and negative for Cytokeratin. Among these forms, high cellularity and microvessel density, high expression of Ki 67 and CD31 and negativity of CD34 prognostic factors for a poor prognosis.

Immunohistochemical assessment of Ki-67 as prognostic cellular proliferation marker in anal canal carcinoma.

In order to define new prognostic factors useful for therapeutic decision-making, the Authors conducted a study on anal canal carcinomas in which Ki-67 proliferation index is correlated with pathological variables and clinical outcome. The Ki-67-detectable antigen is expressed in all stages of the cells cycle except G0. Thus, Ki-67 index can measure cell proliferation and it could be considered an indicator of prognosis. Thirty-one patients with anal canal carcinoma were evaluated. The specimens were formalin-fixed, paraffin-embedded and used for immunostaining of Ki-67 antigen. We found a significant correlation between Ki-67 score and depth of invasion and lymph node involvement. No correlation was found between high Ki-67 value and neoplastic relapse. These results suggest that Ki-67 positivity carries different significance in different cancers. Additional studies are required to ascertain whether more aggressive therapeutic procedures should be applied in the subset of patients with a high growth fraction.

Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.

To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.

Human papillomavirus infection and p53 nuclear overexpression in anal canal carcinoma.

The product of HPV E6 and E7 genes is able to inactivate both the p53 and pRb proteins. The aim of this study was to evaluate the correlation among anal HPV infection and nuclear p53 overexpression. The Authors evaluated HPV DNA by PCR and p53 nuclear expression by immunohistochemistry in 12 cloacogenic and 6 squamocellular carcinoma. HPV DNA was detected in 71.4% of the squamocellular tumors and in 57.1% of the cloacogenic tumors. In squamocellular tumors HPV types 31-33 and 16 were found; in cloacogenic tumors type 16 alone was detected. Nuclear accumulation of p53 was found to be associated with the presence of HPV. There was no significant difference in parietal infiltration, lymph nodes involvement and prognosis between HPV+p53+ patients and HPV-p53- patients. Tumor aggressiveness is likely to be enhanced by factors other than HPV infection and p53 overexpression.

Benign schwannoma of the obturator nerve: a case report.

We describe a schwannoma of the obturator nerve in a woman 66 years old. It was diagnosed only postoperatively because of the aspecificity of the symptoms. The difficulty of making a correct diagnosis during surgery is discussed, and the potential serious consequences of total excision of the nerve are described.

The prevalence of p53 immunoreactivity in anal canal carcinoma.

We examined the relationship between p53 expression and clinicopathologic parameters in anal carcinoma. p53 immunoreactivity was detected in 14/18 (77.7%) tumors. Significant association was found between p53 expression and depth of invasion. There was no significant association between p53 expression and histologic type, lymph node metastasis, age and prognosis. Possibly the genetic pathway to anal carcinoma involving p53 gene overexpression confer aggressive growth pattern, but it does not result in worse prognosis. The absence of correlation between p53 overexpression and prognosis could be explained by tumors negative for mutations having an excess of wild-type p53 protein.

An unusual location of cloacogenic carcinoma.

A 61 year-old female presented with abdominal pain, rectal bleeding, mucus discharge, tenesmus and constipation. Rectal examination and proctoscopy demonstrated rectal stenosis at 5 cm from the anal verge. Transrectal ultrasonography detected a capsulated lesion as a mesenchymal rectal tumor. Computed tomography and endorectal magnetic resonance detected a mesenchymal lesion in the lower-middle rectal thirds. Serum TPA, GICA, SCC and CYFRA were pathological. At surgery the tumour was fixed to the levator ani muscle with rectal folding. Frozen sections of the levator ani muscle biopsies revealed cloacogenic tumour. Abdominoperineal resection was performed. The rectal lesion was cloacogenic carcinoma at 9 cm from the dentate line (pT4 pN0; Ki67 35%; CD31 181 vessels/mm2). Adjuvant radio-chemotherapy was performed. The patient is alive and disease free at 19 months. Extra-anal cloacogenic tumours are an unusual finding. Perhaps cloacal cells were originally present in the rectal wall, but secondary rectal involvement by cloacal remnant from the levator ani muscle cannot be excluded.

Modifications of interphasic NORs as a diagnostic parameter of atypical lesions of the female breast.

Seventy-five breast samples including normal tissue, hyperplastic, metaplastic, atypical and neoplastic lesions were employed for the determination of interphasic Nucleolar Organizer Regions (NORs) modifications and Proliferating Cell Nuclear Antigen (PCNA) immunoreactivity. Interphase NORs were quantitatively and qualitatively modified in atypical lesions and breast carcinomas, whereas only modifications in the Ag-NORs count were found in benign samples. Our results investigated the nature of interphase NORs in the hope of finding a use for their evaluation in the diagnosis and biological clarification of breast epithelial atypia.

[Primary lymphoma of the rectum: diagnosis and treatment]. / Il linfoma primitivo del retto: diagnosi e trattamento.

The authors report a rare case of primary rectal lymphoma non Hodgkin in a young non HIV infected man. Preoperative diagnostic problems, the standards for classification and staging and the proper treatment are briefly discussed. The importance of an accurate histological and immunohistochemical study on preoperative multiple biopsies for a correct diagnosis, staging and treatment, are emphasised in this report.

Technetium-99m sestamibi: an indicator of breast cancer invasiveness.

As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with 99mTc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revision showed a positive 99mTc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm2 and one showed 99 microvessels/mm2; by contrast there were 71.6 +/- 12.1 microvessels/mm2 in the nine N- and sestamibi-negative tumours. Our study suggests that 99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour.