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E Giarnieri

Publications and source records attributed to E Giarnieri.

16 recordsLinked to original sources
PubMed2001

[Genetics-based prognosis evaluation of patients surgically treated for sporadic colorectal cancer].

The basic assumption as rationale of this research was that DNA repair genes (MMR system) are at beginning of the genetic mutational cascade causing the induction of oncogenesis of sporadic colorectal cancers as well as their multiclonal heterogeneity. In a previous study the Authors randomly selected, from a series of 256 patients, 29 patients up to the age of 60 years who underwent surgery for colorectal carcinoma with radical intent. All selected cases were considered as sporadic cancers from a clinical point of view, since none of them fulfilled the Amsterdam criteria for HNPCC and familial adenomatous polyposis was included too. Mismatch repair gene proteins expression and, in particular, gene hMSH2 protein was investigated by immunohistochemistry analysis. In 12 cases (41.4%) hMSH2 exhibited strong expression in the tumoral cells as well as in the surrounding mucosa and at distant mucosa. In 14 cases (48.3%) loss of hMSH2 protein expression was observed in tumoral cells and low immunoreactivity was detected in peritumoral mucosa while strong hMSH2 expression was observed in distant mucosa. In a third small group of patients (10.3%) loss of hMSH2 protein expression was detected in tumoral, adjacent and at distance normal mucosa. After a five years follow up, 100% of twelve patients of first group are still alive vs 64.3% of fourteen patients of second group, while in the third group only one patient survives. These results support the hypothesis of an involvement of hMSH2 gene defect in development of a subset of sporadic colorectal cancer. For the patients with strong expression of hMSH2 in the tumoral cells as well as in the surrounding mucosa and at distant mucosa, this parameter could represent an independent criterion for a good prognostic value.

Colorectal Neoplasms↗
PubMed2000

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.

Aged↗
PubMed2000

Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix.

To analyze relevant factors and their effects on neoplastic progression in cervical carcinoma, a panel of genetic markers was studied. Paraffin-embedded tissue sections were obtained from 37 patients with carcinoma of the uterine cervix, 14 noninvasive squamous cell carcinomas (NISCCs), and 23 invasive squamous cell carcinomas (ISCCs). Immunoreactivity of Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. Positive staining of Msh2 was detected in 13 of 14 (92.9%) NISCCs and in 13 of 23 (56.5%) ISCCs (P < 0.02). Mlh1 immunoreactivity was observed in 10 of 14 (71.4%) NISCCs and in 8 of 23 (34.8%) ISCCs (P < 0.04). Overexpression of p53 protein was found in 4 of 14 (28.6%) NISCCs and in 16 of 23 (69.6%) ISCCs (P < 0.02). Bcl-2 overexpression was detected in 2 of 14 (14.3%) NISCCs and in 15 of 23 (65.2%) ISCCs (P < 0.003). No significant difference in the two types of lesion was found for Bax and Fhit expression. The relationship between Mlh1, Msh2, and p53 protein expression was significant (P < 0.001 and P < 0.001, respectively), as was that between Fhit and Bax immunoreactivity (P < 0.02). In conclusion, we consider that altered expression of Msh2, Mlh1, p53, and Bcl-2 may be a critical event during cervical cancer progression, whereas Fhit may be a component of a proapoptotic pathway.

Acid Anhydride Hydrolases↗
PubMed1999

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.

Aged↗
PubMed1997

Early stage human colorectal cancer: prognostic value of nm23-H1 protein overexpression.

Nm23 gene codifies for a nucleoside diphosphate kinase allowing the intracellular transduction of the signals. In colorectal cancer nm23 protein expression seems related to the progression of the disease. By immunohistochemistry we have studied the intracytoplasmatic nm23 H1 protein expression in 20 patients affected by colorectal cancer at initial stage. In 12 cases it resulted elevated and in four the disease recurred. The overexpression was not correlated with other prognostic factors. Nm23 H1-positive patients affected by colorectal cancer at initial stage could be considered at risk for disease recurrence and included in a more frequent follow-up protocol.

Adult↗
PubMedDate not supplied

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.

Age Factors↗
PubMedDate not supplied

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.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

[Genetic factors and colorectal cancer: a new approach to clinical experimentation].

The Authors point out the basis for a better characterisation of colo-rectal cancer and precursory lesions. In fact the etiology of familial adenomatous polyposis (FAP), aberrant crypt foci (ACF), hereditary non polyposis colon cancer syndrome (HNPCC) seems to be correlated to molecular pathology. Therefore the Authors review colo-rectal cancer natural history which frequently appears to be not related to clinical evolution.

Colorectal Neoplasms↗
PubMedDate not supplied

Intratumoral heterogeneity in colorectal carcinoma: trucut sampling for DNA ploidy analysis.

BACKGROUND: Solid tumors, such as colorectal carcinomas, consist of cell subpopulations that differ both genetically and in their clinical behavior. Many authors have examined cell kinetics and DNA content in colorectal tumors in correlation to clinical and pathological variables with different results. The interpretation of those results present some difficulties related to tumor heterogeneity that to date are unsolved. Our study is based on a new method of colon cancer sampling for DNA content determination. The aim of this work was to reduce the risk of incorrect DNA evaluation due to tumor heterogeneity. MATERIAL AND METHODS: Our study was based on eleven selected cases of T3 colorectal carcinoma. Fresh surgical specimens from the primary tumor site were taken during surgery. For each case at least four samples were taken using a 23 gauge trucut from the outside of the serosa through the tumor to the lumen of the colon. The specimens were stained according to a modified Feulgen method and DNA content was measured by image analysis. Three parameters were evaluated: DNA index, ploidy and proliferation level (considered as the sum of elements corresponding to the S and G2 phases). RESULTS: One of the eleven (9.1%) tumors showed a diploid pattern; four out of eleven (36.4%) cases showed a tetra/polyploid pattern and six out of eleven (54.5%) cases showed an aneuploid pattern. Three tumors were monoclonal (27.3%), one diploid and two aneuploid. Eight were polyclonal (72.7%). Considering the single specimen, seven out of sixty-eight specimens (10.3%) were inadequate because of scanty material. Twenty-five out of the sixty-one adequate specimens (41%) were monoclonal and thirty-six (59%) were polyclonal. Five tumors (three monoclonal and two polyclonal) showed the same cell clones on all the examined samples. The remaining six tumors showed interregional variability. The six of the eight polyclonal cases (75%) multiple stem lines were evident, analyzing only one sample taken close to colon serosa, while in one case (25%) it was necessary to examine two samples in order to see the polyclonality of the lesion. When samples taken close to mucosa where analyzed, however, one sample was not enough to show tumor polyclonality in five of the eight polyclonal examined cases. Proliferation level varied greatly in different parts of the same carcinoma and did not correlate to the site from which the sample was taken. CONCLUSION: In the present study, we demonstrated that DNA ploidy differences may exist between the superficial and the deep part of the same neoplasia and that tumor samples show a greater variability in the deeper layers. Using trucut samplings, it was possible to point out the majority of aneuploid cell populations close to the serosa. In conclusion, trucut biopsy permits full thickness sampling of the tumoral mass and allows, from few samples, to evaluate the multiple DNA stemlines present in different parts of a colorectal tumor.

Aged↗
PubMedDate not supplied

BCL2 and BAX expression in hyperplastic and dysplastic rectal polyps.

BACKGROUND/AIMS: Members of the gene family that includes BCL2 and BAX are functionally antagonists in the apoptosis process and they have been observed in normal and neoplastic tissues. The aim of this study is to investigate the combined effects of BCL2 and BAX protein in normal mucosa, dysplastic and hyperplastic polyps of the rectum. METHODOLOGY: We studied BCL2 and BAX protein expression in 40 cases of adenomatous polyps all located in the rectum, with different dysplastic gradings, and the mean time in 10 cases of normal rectal mucosa. RESULTS: BCL2 expression was found more frequently in hyperplastic and in low dysplastic polyps with moderate and strong positivity compared to moderate and severe dysplasia. BAX expression was found in normal mucosa in hyperplastic and dysplastic polyps, the immunoreactivity was prevalently moderate and strong. CONCLUSIONS: These preliminary data suggest that BCL2 and BAX confirm a probably different role in apoptosis. Nevertheless, it is important to know the relation between the molecular pathways of apoptosis, the defective mismatch repair and the tumor suppressor genes associated with an increased mutation rate in cancerogenesis of the colorectum.

Adenoma↗
PubMedDate not supplied

Altered expression of hMSH2 in sporadic colorectal cancer, surrounding mucosa and at distant colonic mucosa.

BACKGROUND: Mismatch repair gene hMSH2 is involved in correction of mispairing during replication and its mutation is associated both with microsatellite instability and with hereditary colorectal cancer. We evaluated its involvement in sporadic colorectal cancer tumorigenesis too. MATERIALS AND METHODS: The protein expression pattern of hMSH2 was evaluated on 29 cases of resected sporadic adenocarcinoma using an immunohistochemical approach. RESULTS: In 14 cases, lack of hMSH2 protein expression was observed in adenocarcinoma and in peritumoral mucosa. In 12 patients, hMSH2 resulted in strong expression in the tumour as well as in the surrounding mucosa and at distant mucosa. In three cases, hMSH2 protein expression in tumoral, adjacent and at distance normal mucosa resulted negative. CONCLUSION: Repair genes could play an important role in tumour progression and in sporadic colorectal cancer. Detection of protein expression by immunohistochemistry may be a method to select tumours for successive genetic investigations.

Adenocarcinoma↗
PubMedDate not supplied

Overexpression of NDP kinase nm23 associated with ploidy image analysis in colorectal cancer.

The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines with low and high metastatic potential. Nm23 is localized on chromosome 17q21.3-22. Allelic deletions of chromosome 17 have been related to the progression of colorectal carcinomas. We have evaluated and compared the expression of nm23 NPD kinase protein using an immunohistochemical method and DNA ploidy evaluation with image analysis. This study was performed on 20 patients, who underwent surgery for colorectal carcinoma. Patients were followed up during the period from 1992 to 1994. Results have shown an association between the parameters obtained for the nm23 NPD kinase protein expression, and aneuploid DNA and neoplastic progression. The expression of nucleoside diphosphate (NDP) kinase mm23 has been reported to be inversely related to the metastatic potential of experimental cells in human breast cancer. A relationship between the positivity in protein expression of gene product in the allele nm23 H1 and the state of the lymph nodes has also been found.

Colorectal Neoplasms↗
PubMedDate not supplied

Image analysis in multisample biopsy after ileal pouch-anal anastomosis.

Pouchitis in ileal anal anastomosis represents an important clinical complication after restorative proctocolectomy. Acute and chronic inflammation of the reservoir is a frequent event sometimes associated with villous atrophy and colonic metaplasia. After ileal pouch anastomosis, twenty-one patients affected by ulcerative colitis were studied. An image analyzer CAS 200 (Becton Dickinson) was utilized to evaluate the DNA intranuclear content in every biopsy. In two cases abnormal DNA distribution was observed, and in one case a poliploid pattern was seen. Abnormal DNA distribution was also present in colonic metaplasia. Therefore, image analysis for the detection of DNA aneuploidy may be of additional value together with histologic parameters in follow up, in order to exclude transformation of the ileal mucosa in neoplastic epithelia.

Adolescent↗
PubMedDate not supplied

Restorative proctocolectomy: histological assessment and cytometric DNA analysis of ileal pouch biopsies.

BACKGROUND/AIMS: The pathological changes and the risk of developing cancer in the ileal pouch mucosa of patients who received restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) were studied. The presence or absence of remaining rectal mucosa below the IPAA in both patients with stapled and handsewn IPAA was also examined. MATERIALS AND METHODS: Endoscopy of the ileal pouch was performed on 38 patients at 4, 12, 18 and 36 months after restorative proctocolectomy with ileal pouch. Mucosal biopsy specimens were taken from the ileal reservoir in order to assess the histological incidence of inflammation. In 23 patients, biopsies were taken to perform cytometric DNA analysis. Clinical symptoms of pouchitis (over six evacuations in 24 hours, night-time evacuations, leakage of feces, bloody diarrhea, abdominal pain and fever) were recorded and correlated with the histological findings. Biopsies were also sampled below the ileo-anal anastomosis (IPAA) in order to identify residual rectal mucosa. RESULTS: Results of histological assessment showed various degrees of chronic inflammation increasing over time (from 42 to 60%) while the presence of both acute and chronic inflammation of the reservoir was less frequent (from 18 to 30%). Villous atrophy was present in 39-68% of patients and the grade of villous atrophy was correlated to the grade of inflammation. Clinical pouchitis was present in 3 to 8% of cases at the different controls and it was always associated with the highest grade of histological inflammation and severe villous atrophy. No significant alteration of the DNA cellular content was observed. Very low incidence of aneuploidy (0.7-1% Ex.R.) has been reported in three cases. However, we found dysplasia in only one patient who underwent surgical treatment for familial polyposis coli. IPAA evaluation showed no residual rectal mucosa in 40% of cases with stapled IPAA; in the remaining 60%, we found a small amount of rectal mucosa (maximum 1 cm). We did not find rectal mucosa after handsewn IPAA with mucosectomy. CONCLUSIONS: Patients treated with restorative proctocolectomy with IPAA showed a higher and increased incidence of inflammation during follow-up. No significant alteration of DNA cellular content nor dysplasia of the pouch mucosa were observed. In this study the chance of leaving rectal mucosa after stapled IPAA was about 60%.

Adolescent↗
PubMedDate not supplied

[Is it possible to consider intranuclear DNA imaging analysis as a new parameter in the staging of colorectal cancer?].

Intranuclear DNA imaging may be considered as a marker of the biological behaviour of neoplasias. However, some questions fundamentally related to the interpretation of cytometric data, to the correlation with other histomorphological parameters and to tissue sampling concerning staging and prognostic evaluation of colon cancer patients are still unsolved. A way to solve this problem may be to perform multiple full thickness samplings.

Cell Nucleus↗