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Biomedical subjects

D Cabibi

Publications and source records attributed to D Cabibi.

13 recordsLinked to original sources

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.

Antigens, Neoplasm↗

Prevalence of vulval lichen planus in a cohort of women with oral lichen planus: an interdisciplinary study.

BACKGROUND: Lichen planus (LP) is a mucocutaneous inflammatory dermatosis that frequently involves the oral and genital mucosae. Patients with LP affecting these sites are often seen by oral medicine specialists or gynaecologists who work in isolation and depend heavily on histopathologists to help them in confirming the diagnosis. There are few studies in the literature combining the experiences of these specialists who share the care of patients with both oral and genital LP. OBJECTIVES: To estimate the prevalence of vulval LP (VLP) in a cohort of patients with histologically confirmed oral LP (OLP). METHODS: The study group consisted of 42 women histologically diagnosed with OLP. The mean age was 60.5 years (range 27-81). They underwent genital examination, colposcopy and vulvoscopy. For the histological confirmation of clinical VLP biopsies were performed whenever a clinical lesion was found. Oral and genital biopsy specimens were processed through histological and immunohistochemical staining. Histological diagnoses of LP were made according to the modified World Health Organization histopathological criteria proposed by van der Meij and van der Waal for the diagnosis of OLP, and extended to VLP. Patients with clinical evidence, but without the histological confirmation of OLP and VLP, were excluded from the study group. RESULTS: Thirty-two vulval and one vaginal biopsy specimens were obtained. Histological diagnoses were confirmed in 24 of 32 (75%) patients who underwent a vulval biopsy: these represent 57% (24 of 42) of the study group. Of the 12 patients free of symptoms such as itching, burning and dyspareunia, but with clinical vulval lesions, 11 (92%) had histological confirmation of VLP. Vulval lichen sclerosus was ascertained in five of 32 (16%) cases. CONCLUSIONS: This study showed a 57% prevalence of VLP in selected patients with OLP. The high prevalence of VLP of 92% in the women who were free of vulval symptoms confirmed the usefulness of this careful integrated approach.

Adult↗

[A gastric polypoid signet ring cell carcinoma].

AIM: The authors signal a case of gastric polypoid signet ring cell carcinoma, of particular interest for its rarity like show from the review of the literature, which is the first to have been described after Tabaru's citation. METHODS: The study has been carried out at the Department of Surgical and Oncological Sciences of the University of Palermo. It has been based on 2000 cases analysed from June 2001 to December 2003. RESULTS: The authors advance some and emphasizes the diagnostic flow chart and therapeutic choices adopted. CONCLUSIONS: We agree that the endoscopic polypectomy is surgical procedure of first approach, but modifying the therapeutic guideline in relation to histologic examination, like happened in the case in issue.

Adult↗

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.

Adult↗

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.

Adenocarcinoma↗

[Correlations between morphometric characteristics and the presence of lymph node metastasis in stage T1 and T2 breast carcinoma].

In this study the relationship between cyto-morphometric characteristics of breast cancer and lymph node status was investigated. The study was conducted on 20 cases of T1-T2 breast cancer with node metastasis and 20 cases of T1-T2 breast cancer without node metastasis. About 100 nuclei for each patient were analyzed by means of a computerized image analyzer, and mean nuclear diameter, mean nuclear area, mean form factor and number of cells in 8 classes of diameter were studied. Mean mitotic index was also calculated. No statistic difference was found for all these variables, between the two groups. In conclusion, cyto-morphometric parameters although often represent an index of aggressiveness, they are not related to lymph node status. This one is, in fact, only an indicator of tumor's ability to spread, and tumor's diffusion can occur through different ways from the lymphatic one.

Breast Neoplasms↗

Interactive computerized morphometric analysis for the differential diagnosis between dysplasia and well differentiated adenocarcinoma of the prostate.

To distinguish prostatic dysplasia (or adenosis) from well differentiated adenocarcinoma on transrectal needle biopsy, a morphometric study was conducted on 20 cases of adenosis and 20 cases of well differentiated adenocarcinoma of the prostate. About 100 cells for each patient were analyzed by means of a computerized image analyzer, and mean nuclear diameter, mean nuclear area, mean form factor and number of cells in eight classes of nuclear diameter were studied. The best predictors of malignancy (evaluated by means of Receiver Operating Characteristics curves) were mean nuclear area greater than 28 mu2, presence of more than 5% of cells with nuclear diameter greater than 6.15 mu, and mean nuclear diameter greater than 5 mu. Using these diagnostic criteria the probability of malignancy for a positive specimen rises from 14% (pre-test) to 75% (post-test).

Adenocarcinoma↗

Thymidylate synthase gene promoter polymorphisms are associated with TSmRNA expressions but not with microsatellite instability in colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biological characteristic of most tumours, being involved in 85% of hereditary non-polyposis colorectal cancer (HNPCC). It also occurs in 10-15% of sporadic colorectal cancers (CRC). HNPCC appears to be caused by germline mutations in mismatch repair (MMR) genes, which are responsible for repairing single base-pair mismatches. MSI is also associated with a better response of CRC to adjuvant chemotherapy with fluoropyrimidines. We investigated any relationship between the MSI status and the TSmRNA expression, the polymorphisms of 5-Fluorouracil (5-FU cellular target, the enzyme thymidylate synthase (TS) and TS expression evaluated by means of immunohistochemistry. MATERIALS AND METHODS: A series of 80 colorectal cancers was evaluated for MSI and polymorphisms in the 3'UTR and the 5'UTR of the TS gene by a PCR assay. TSmRNA was quantified by real-time PCR and the TS expression by immunohistochemical assay. RESULTS: There was no significant association between the polymorphisms in the TS gene and the MSI or between the TSmRNA expression and the MSI status. CRC with a 3R/3R or 2R/3R genotype showed a significantly higher TSmRNA expression than those with the 2R/2R genotype (p = 0.001 and p = 0.028, respectively). Another significant association was found between the TSmRNA expression and the TS immunohistochemical determination (p = < 0.05). No association was found between the polymorphism of the 3'UTR and the TSmRNA expression. CONCLUSION: Our data show that there is no association between MSI status and the polymorphisms in the 3' and 5' UTRs and the TS expression. Tumour samples displaying the 3R/3R or 2R/3R genotype of TS have higher TSmRNA levels than the 2R/2R genotype. Polymorphic variant of the 3'UTR does not influence the TSmRNA level. We found a relationship between the TSmRNA expression, evaluated by real-time PCR, and with the TS level determined by immunohistochemical assay. Thus, genotyping of the 5'UTR and quantification of the TSmRNA expression in human CRC could be considered as predictors for response to SFU-based chemotherapy. The evaluation of the TS expression by means of immunohistochemistry assay remains a safe and reliable assay in CRC.

5' Untranslated Regions↗

Lymph node metastases displaying lower Ki-67 immunostaining activity than the primary breast cancer.

UNLABELLED: The aim of the study was to verify by Ki-67 immunostaining if any difference exists in the cell proliferating fraction between primary breast tumors (PTs) and matching positive axillary lymph nodes (ALNs). PATIENTS AND METHODS: Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in 160 node-positive breast carcinomas and in their respective lymph node metastases. RESULTS: An increase of Ki-67 immunoreactive cells in ALN compared with that of PTs was observed in 84% of cases (ALN: mean 17%, PTs: mean 8%; p < 0.001), whereas 16% of the cases showed Ki-67 value two to six times lower in the ALNs than in the corresponding PTs (ALN: mean 3.2%, PTs mean 12.5%; p < 0.005). The decrease of Ki-67 positive cells in the ALN was independent from the histotype and the histological grade of the tumor. CONCLUSION: A different cell proliferation fraction between PTs and matching positive ALNs was demonstrated and underlined that the existence of a group of patients with decreased number of Ki-67 immunoreactive cells in lymph node metastases compared with that of the primary tumors could be taken into account in the choice of therapeutic strategy.

Breast Neoplasms↗

Biologic effects of ultrasound on liver cells of rat embryos.

Experiments on the biologic effects of ultrasound (US) were carried out on rat embryos exposed for 120 s to a US beam showing features similar to those already employed for diagnostic purposes. Electron microscopic investigation of the liver parenchyma of rat embryos confirmed results obtained from adult guinea pigs with the same duration of exposure, i.e. diffuse vacuolization of cytoplasma and varying degrees of mitochondrial damage.

Animals↗