Difference in Ki67 and thymidylate synthase expression in primary tumour compared with metastatic nodes in breast cancer patients.

Breast cancer is a heterogeneous disease, so therapeutic predictive biological markers need to be identified. To date an accurate evaluation of predictive markers is mainly done at the primary site; however, the main goal of adjuvant therapy for breast cancer is the control of micrometastases. The aim of this study is to assess as therapeutic and/or prognostic marker, the proliferation status of primary tumors and involved nodes as measured by Ki67 and thymidylate synthase (TS) expression, in 30 breast cancer node positive patients. TS is the main target of 5-fluorouracil (5-FU) activity, and its overexpression is one of the mechanisms of 5-FU drug resistance; however, in some studies its absence is responsible for a worse response to 5-FU. Our results show that malignant cells of involved nodes were in a post mitotic phase of the cell cycle, and show a low proliferation index and TS expression, while the primary tumours and controls, were strongly positive. On these basis we can hypothesize that these cells could be less sensitive to 5-FU. Further studies are necessary to identify other mechanisms responsible for their metastasing capability and/or for their aggressiveness.

Clinical relevance of thymidylate synthase expression in the signet ring cell histotype component of colorectal carcinoma.

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas.

Biological aggressiveness evaluation in prostate carcinomas:immunohistochemical analysis of PCNA and p53 in a series of Gleason 6 (3+3) adenocarcinomas.

We selected 63 prostate tumors with Gleason's grade 6 (3+3), commonly showing both tubular and cribrous patterns. We compared in both patterns the expression of two of the most used biologic markers: PCNA and p53, with the aim to verify the validity of the Gleason's grading system to compare the morphologic grade with biologic aggressiveness and prognostic value. We did not find any statistical difference in the protein immunopositivity, indicating that both patterns could have identical biologic behaviour; then we confirmed the validity of Gleason's system for considering both tubular and cribrous patterns as an intermediate grade of tumoral differentiation. Moreover, we found a linear relationship between the increase of PCNA and the accumulation of mutated p53; this datum could confirm the hypothesis that p53 mutation is a late event in prostate carcinogenesis.

[Procollagen III and laminin in chronic viral hepatopathies]. / Procollagène III et laminine dans les hépatopathies chroniques d'origine virale.

OBJECTIVES: We measured serum concentrations of the N-terminal peptide of type III procollagen (PIIIP) and laminin (Lam-P1) in patients with chronic viral liver disease in the various stages of the clinical course, to judge their value in assessing liver fibrogenesis, and also compared them with a number of liver function tests and histological scores of inflammation and fibrosis. METHODS: Twenty-nine patients with chronic persistent hepatitis, 39 with chronic active hepatitis and 42 with liver cirrhosis were studied. The control group was composed of 45 healthy blood donors. Serum PIIIP and Lamp-P1 were determined by radioimmunoassay; hepatic function was measured by routine assay; liver fibrosis and inflammation were graded on a 0-3 score scale. RESULTS: A significantly higher increase in serum levels of PIIIP and Lam-P1 was found in the liver cirrhosis group compared with the other groups (p < 0.05). Serum PIIIP correlated with transaminase levels in the chronic active hepatitis group and with gammaglobulin and total bilirubin in the liver cirrhosis group. A positive correlation was found only with gammaglobulin and total bilirubin in the cirrhosis group. A positive correlation was found between serum PIIIP levels and the rating scale of liver necrosis. In contrast, for Lam-P1 values, a correlation with the rating scale of necrosis and fibrosis was found. CONCLUSION: Our findings confirmed the increase of PIIIP and Lamp-P1 in chronic viral liver disease, but because of the frequent overlap values, they cannot be used as substitutes for liver biopsy for diagnosis. The correlations with the histological findings indicate that these two markers can be used during the follow-up of patients receiving anti-inflammatory or anti-fibrotic treatment.

[Leiomyoma of the nipple]. / Il leiomioma del capezzolo.

A case of 28 years woman with nipple's leiomyoma we report. Only 38 cases are reported in the literature. This neoplasm presents a difficult differential diagnosis with the remaining flogistic and neoplasm breast and nipple disease.

[Serum variations of 2 markers of fibrogenesis in chronic hepatitis C treated with alpha interferon]. / Variazioni sieriche di due marcatori di fibrogenesi in corso di epatiti croniche C trattate con alfa interferone.

We evaluated variations in serum levels of N-terminal peptide of type III procollagen (PIIIP) and laminin (Lam-P1) in 36 anti-HCV positive patients, confirmed by RIBA II, with chronic hepatitis treated with alpha interferon (IFN) at a dose of 6 million units (MU) three times for week for 6 months, followed by 3 MU three times for week for a further 6 months. We consider responders (R) those patients who after one year of therapy had normalized ALT levels, and non-responders (NR) the remaining subjects. Serum PIIIP and Lam-P1 were determined by RIA on entry to the study and at 12 months. Ten patients underwent a percutaneous liver biopsy also at the end of the therapy for the histological evaluation of the necroinflammatory activity and fibrosis according to the Knodell score system. Overall, at the end of therapy, the mean levels of both markers were lower than at entry to the study, with a statistically significance only for the Lam-P1 values (p < 0.05). When, however, we divided the patients into R (n = 15) and NR (n = 21) subgroups, the mean baseline values of both markers were significantly higher in NR vs controls and after therapy there was a significantly reduction only for PIIIP values (p < 0.01). In the group of R there is a slight, but not significantly reduction of both markers. The comparison of the Knodell's score before and after IFN treatment showed an improvement of the necroinflammatory activity, but not of fibrosis. In conclusion patients R to IFN therapy have lower baseline values of PIIIP and Lam-P1 than NR and therapy with IFN improves the serum values of PIIIP as well as the score of the necroinflammatory activity.

Metastasis of high grade renal cell carcinoma, clear cell type, in fibrous dysplasia with superimposed giant cell reparative granuloma.

A case of monostotic fibrous dysplasia in a 54-year-old male complaining of severe pain in the right hip is presented. Imaging findings demonstrated an extremely aggressive lesion involving bones, liver, lungs, and lymph nodes, and suggested the possibility of sarcomatous transformation. Histological examination established a diagnosis of metastatic high-grade renal carcinoma, clear cell type, and demonstrated the presence of superimposed giant cell reparative granuloma. This latter is a rare example of giant cell reparative granuloma arising in a long bone and in association with fibrous dysplasia. The clinical, radiographic, and histopathologic features of fibrous dysplasia and giant cell reparative granuloma are discussed.

Sudden coronary death, fatal acute myocardial infarction and widespread coronary and myocardial inflammation.

BACKGROUND: T-lymphocyte activation within atherosclerotic plaque, and widespread to the myocardium, has been shown in patients with acute coronary syndromes. OBJECTIVE: To investigate the presence of T-lymphocyte infiltrate at different stages of acute coronary syndromes by studying patients with sudden coronary death, acute myocardial infarction (AMI) and healed infarction, in comparison with patients with myocarditis and patients with non-ischaemic heart failure. METHODS: 72 cases were studied at autopsy: 12 dying of sudden coronary death (group 1), 12 dying <4 weeks (group 2) and 12 dying >4 months after AMI (group 3), 12 with active lymphocytic myocarditis (group 4), 12 with hypertensive heart disease (group 5), and 12 control subjects (group 6). Light microscopy was performed to measure the number of activated T-lymphocytes (CD3+/DR+) in the myocardium and coronary artery wall, and intercellular adhesion molecule-1 (ICAM-1) expression in the myocardium. RESULTS: Activated T-lymphocyte infiltrates and ICAM-1 myocardial expression in both remote and peri-infarction regions and activated T-lymphocytes within the epicardial coronary artery wall of both the infarct- and non-infarct-related arteries were found in groups 1, 2 and 3, whereas myocardial, but not coronary, infiltrates were found in groups 4 (p<0.001 vs groups 1, 2 and 3 for coronary infiltrates). Groups 5 and 6 had no evidence of myocardial or coronary inflammation (p<0.001 vs groups 1, 2 and 3). CONCLUSIONS: The study shows the presence of a lymphocytic infiltrate in both coronary arteries and myocardium and a proinflammatory phenotype shift in the myocardium associated with acute coronary thrombosis in patients dying suddenly, shortly, or even late after coronary thrombosis.

A diagnostic trap for the dermatopathologist: granulomatous reactions from cutaneous microimplants for cosmetic purposes.

We present a case of late granulomatous reactions from silicone that first appeared in a site different from that of the injection causing an incorrect diagnosis of liposarcoma in the beginning. The histological picture was a cystic-macrophagic granuloma in both the injection site (upper lip) and the migrating site (paranasal regions). We think that the foreign body has undergone an antigravity migration from the upper lip to the right paranasal region. To our knowledge, such a phenomenon has not been yet reported in literature.

[Breast cancer and lymph node metastasis: relation of lymph node dimensions and metastasis]. / Carcinoma mammario e metastasi linfonodali: rapporto fra dimensioni dei linfonodi e delle metastasi.

The Authors have examined 1159 lymph nodes obtained from 64 cases of breast carcinoma to value the presence of a correlation between the insurgence of metastases and lymph node dimensions. Metastases were more frequent in larger lymph nodes. Nevertheless, metastases were also present in small (< 5 mm) or very small (< 2 mm) lymph nodes. This indicates the importance to carefully examine small lymph nodes during gross examination and to obtain multiple sections from them.

[Peripheral neuropathy during ocular myopathy: description of a case]. / Neuropatia periferica in corso di miopatia oculare: descrizione di un caso.

A case of ocular myopathy view presents only slight subjective symptoms, but a wide range of objective manifestations. The clinical features, but above all the morphological aspects of the muscle and the peripheral nerve presented by the patient, are briefly discussed, also in view of possible pathogenetic correlations.