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C De Micco

Publications and source records attributed to C De Micco.

At least 19 recordsLinked to original sources
PubMed2006

Expression of tpo mRNA in thyroid tumors: quantitative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes.

Immunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P < 0.0001; R = 0.59) and showed that overall tpo expression was lower in all carcinomas than in normal and BT (P < 0.05). The ratio tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar gamma1 rearrangement was correlated with qualitative changes in tpo mRNA (P < 0.01). These results confirmed the decrease of TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.

Adult↗
PubMed2005

[Abrikossoff tumor of the proximal esophagus misdiagnosed as a thyroid nodule].

The diagnosis of thyroid nodules is straightforward and rarely mistaken. We present a case of a paraesophageal granular cell tumor, discovered incidentally during surgery for what it was diagnosed as a suspicious thyroid nodule by ultrasound and FNA. Complete resection was achieved without disruption of the esophageal mucosa. A terminal branch of the recurrent laryngeal nerve had to be resected en bloc with the tumor. Morphological and immunohistochemical diagnosis was established postoperatively. A review of the literature is presented.

Adenocarcinoma↗
PubMed2005

Lymph node involvement in macroscopic medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare disease, with variable tendency to lymphatic spread. The aim of this retrospective study was to identify distinctive features of large MTC with and without nodal metastases. METHODS: Between 1993 and 2003, 28 consecutive patients underwent total thyroidectomy and neck node dissection for sporadic MTC larger than 10 mm in diameter. RESULTS: All tumours were confirmed to be malignant with a locally invasive pattern of growth. Lymph node metastases were present in 16 patients (N1) and absent in 12 (N0). There were no statistically significant differences between patients with N0 and N1 tumours concerning age (mean 52.1 versus 53.4 years), male:female ratio (0.7 versus 1.0), basal preoperative calcitonin concentration (mean 3238 versus 3076 pg/ml) and tumour size (23.3 versus 23.9 mm). There were differences in the incidence of tumour invasion (P < 0.001), vascular embolism (P = 0.011) and peritumoral thyroiditis (P = 0.039). Measurement of basal and stimulated calcitonin levels after surgery confirmed biochemical cure in all patients with N0 tumours and half of those with N1 disease (P = 0.006). CONCLUSION: There were no preoperative factors that predicted node status for MTC larger than 1 cm in this series. Total thyroidectomy and nodal dissection remains the optimal treatment.

Adolescent↗
PubMed2005

ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients.

Like children exposed to Chernobyl fallout, the workers who cleaned up after the accident, also known as liquidators, have exhibited an increased incidence of thyroid cancer. A high prevalence of ret/PTC3 rearrangement has been found in pediatric post-Chernobyl thyroid tumors, but this feature has not been investigated in liquidator thyroid tumors. In this study we analyzed the prevalence of ret/PTC1 and ret/PTC3 in thyroid tumors from 21 liquidators, 31 nonirradiated adult Ukrainian patients, and 34 nonirradiated adult French patients. ret rearrangements in carcinomas were found in 83.3% of liquidators, 64.7% of Ukrainian patients, and 42.9% of French patients. The prevalence of ret/PTC1 was statistically similar in the three groups. The prevalence of ret/PTC3 was significantly higher in liquidators than in French patients (P = 0.03) but it was also high in nonirradiated Ukrainian patients who exhibited values intermediate between liquidators and French patients. In adenomas the prevalence of rearrangement was significantly higher in all Ukrainians than in French patients (P = 0.004). Like children exposed to Chernobyl fallout, liquidators showed a high prevalence of ret/PTC3. This finding suggests that irradiation had the same effect regardless of age. However, given the high rate of ret/PTC3 in nonirradiated adult Ukrainians, the possibility of genetic susceptibility or low-level exposure to radiation in that group cannot be excluded.

Adult↗
PubMed2004

Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer.

INTRODUCTION: Akt activation is involved in the pathogenesis of inherited thyroid cancer in Cowden's syndrome and in sporadic thyroid cancers. In cell culture, Akt regulates thyroid cell growth and survival; but recent data suggest that Akt also regulates cell motility in non-thyroid cell lines. We therefore sought to evaluate the role of Akt in thyroid cancer progression. METHODS: We evaluated 46 thyroid cancer, 20 thyroid follicular adenoma, and adjacent normal tissues samples by immunohistochemistry for activated Akt (pAkt), Akt 1, 2, and 3, and p27 expression. Immunoblots were performed in 14 samples. RESULTS: Akt activation was identified in 10/10 follicular cancers, 26/26 papillary cancers, and 2/10 follicular variant of papillary cancers, but in only 4/66 normal tissue samples and 2/10 typical benign follicular adenomas. Immunoactive pAkt was greatest in regions of capsular invasion; and was localised to the nucleus in follicular cancers and the cytoplasm in papillary cancers, except for invasive regions of papillary cancers where it localised to both compartments. Immunoactive Akt 1, but not Akt 2 or Akt 3, correlated with pAkt localisation, and nuclear pAkt was associated with cytoplasmic expression of p27. In vitro studies using human thyroid cancer cells demonstrated that nuclear translocation of Akt 1 and pAkt were associated with cytoplasmic p27 and cell invasion and migration. Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition. DISCUSSION: These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression.

Adenoma↗
PubMed2001

[Immunodetection of thyroid peroxidase in the diagnosis of follicular variants of thyroid papillary cancer].

STUDY AIM: The aim of this retrospective study was to assess the role of thyroid peroxidase immunodetection in the cytological diagnosis of follicular variants of thyroid papillary cancer (FVTPC) which are difficult to identify by standard cytology. PATIENTS AND METHODS: Between 1991 and 1998, 3,505 thyroid fine needle aspiration biopsies were performed by thyroid peroxidase immunocytochemistry and 1,576 patients were operated on. Out of a total of 227 thyroid papillary cancers (TPC), 42 (18.5%) were diagnosed as FVTPC. The results of standard cytology and thyroid peroxidase immunodetection were compared with the histological findings. RESULTS: The rate of false negatives for TPC in standard cytology was 11% (25/227 cases), with 40% of these false negatives being FVTPC; ten out of 42 (23.8%) cases of FVTPC were not identified by standard cytology. However, cytology with thyroid peroxidase immunodetection diagnosed 224 out of the 227 TPC (99%), and all the FVTPC were correctly identified (100%). CONCLUSION: FVTCP are the most frequent source of false negatives in standard cytology. Thyroid peroxidase immunodetection allows most of these errors to be avoided, and correctly identifies 99% of TPC including FVTPC.

Biopsy, Needle↗
PubMed2000

In situ hybridization and immunohistochemistry study of thyroid peroxidase expression in thyroid tumors.

Malignant thyroid tumors reportedly exhibit an anomaly in thyroid peroxidase (TPO) resulting in a lower affinity for monoclonal antibody 47 (mAb 47) in immunohistochemistry studies. The purpose of the present study was to compare TPO immunostaining in normal, benign, and malignant thyroid tissue with expression of mRNA sequences in four exons of the molecule including the epitope of mAb 47. TPO immunostaining was performed using mAb 47 and a polyclonal antibody (pAb). Messenger RNA expression was investigated by in situ hybridization using probes specific for mRNA sequences in exons 2, 12 (epitope of mAb), 15, and 17. As expected, pAb immunostaining was significantly positive on all benign tumors and 50% of carcinomas. With mAb 47, little or no immunostaining was observed in 16 of 17 carcinomas while significantly positive immunostaining was found in normal tissue and benign tumors. In situ hybridization showed a decrease and heterogeneity in the expression of all mRNA sequences in carcinomas as compared to normal tissue and benign tumors. Unlike the other three probes, the probe specific for exon 12 hybridized strongly with benign tumors but poorly with most carcinomas. Poor hybridization was usually correlated with defective mAb 47 immunostaining. These results confirm that TPO is expressed in thyroid carcinomas but in smaller amounts than in normal tissue and benign tumors. In malignant tumors, qualitative changes in TPO may also impede mAb 47 immunostaining. In situ hybridization showed a concomitant decrease in the corresponding TPO mRNA sequence. These changes could be due to abnormalities in the maturation of TPO mRNA leading to a different splicing variant.

Adenocarcinoma, Follicular↗
PubMed1999

The value of thyroid peroxidase immunohistochemistry for preoperative fine-needle aspiration diagnosis of the follicular variant of papillary thyroid cancer.

BACKGROUND: With the use of May-Grunwald-Giemsa staining, cytologic features of the follicular variant of papillary thyroid cancers (FVPTCs) on thyroid fine-needle aspiration (FNA) often resemble those of hyperplastic and adenomatous nodules. Detection of reduced staining after thyroid peroxidase (TPO) immunohistochemistry with monoclonal antibody MoAb47 has been shown to be a helpful diagnostic marker. The purpose of this study was to assess the value of TPO immunohistochemistry for the diagnosis of FVPTC. METHODS: Of 3505 patients with adequate FNA samples, 1576 patients underwent surgical procedures. Histologic examination of the surgical specimen demonstrated papillary thyroid cancer in 227 cases, including 42 FVPTCs (18%). The diagnostic accuracy of standard thyroid FNA and TPO immunohistochemistry, which we use routinely, was compared in these 42 FVPTCs. RESULTS: Standard FNA allowed accurate diagnosis of malignancy in 32 of the 42 FVPTCs and in 170 of the 185 typical papillary thyroid cancers. TPO-immunohistochemistry staining was accurate in all 42 FVPTCs and in 182 of 185 typical PTCs. CONCLUSIONS: FVPTC is a frequent source of false-negative results on standard thyroid FNA. This study shows that TPO immunostaining accurately demonstrates malignancy in these tumors.

Adolescent↗
PubMed1998

Latent subclinical medullary thyroid carcinoma: diagnosis and treatment.

Sporadic medullary thyroid carcinoma (SMTC) is usually diagnosed at a clinical stage often associated with lymph node involvement. Hence surgical treatment does not result in definitive cure in many patients. Studies have demonstrated that routine measurement of serum basal calcitonin (CT) in patients with nodular thyroid disease allows preoperative, early diagnosis of unsuspected SMTC. The aim of this work was to assess the results of surgery in patients operated on for subclinical SMTC detected preoperatively by measurement of serum CT. Results were compared with those obtained in patients with SMTCs diagnosed at a clinical stage and operated on during the same period. During a 4-year period (1993-1996) 24 SMTCs were diagnosed and treated in our department. They were diagnosed at a clinical stage in 13 patients (group 1): palpable thyroid tumor (n = 11), palpable metastatic lymph node (n = 6), distant metastases (n = 4). In nine cases the diagnosis was made by both fine-needle aspiration cytology and serum CT measurement. In the four other cases the initial cytology was incorrect, but the diagnosis was revised on the basis of elevated basal CT values. In 11 patients (group 2) presenting with nodular thyroid disease, SMTC was not clinically detectable. SMTC was preoperatively suspected by elevated CT levels: basal CT > 10 pg/ml and pentagastrin-stimulated CT peak > 100 pg/ml. One patient in group 1 with distant metastases was not operated on. All of the other 12 patients underwent total thyroidectomy and extensive lymph node dissection. The mean size of the tumors was 27 mm. Lymph node involvement was found in nine patients. After surgery, CT levels returned to normal in five patients but remained elevated in five others; the two remaining patients died of distant metastases. All 11 patients in group 2 underwent total thyroidectomy and central neck dissection. None of the 11 patients had nodal extension. All 11 patients are biochemically cured. It was concluded that routine measurement of basal serum CT in those with nodular thyroid disease allows early, preoperative diagnosis of subclinical SMTC and improves the results of surgery.

Adult↗
PubMed1998

Comparison of thyroid peroxidase expression with cellular proliferation in thyroid follicular tumors.

Thyroid cancer is associated with abnormal thyroid peroxidase (TPO) expression as shown by abolition of immunodetection by monoclonal antibody 47 (Mab 47). The purpose of this study was to determine the relation of this abnormality with differentiation and proliferative potential of follicular tumors evaluated by analyzing thyroglobulin (TG) expression and proliferative cell nuclear antigen (PCNA) index. TPO, TG, and PCNA immunostaining were performed in a series of 30 thyroid follicular tumors ranging from adenoma to invasive carcinoma. Our findings confirmed that TPO abnormalities and PCNA index were correlated with malignancy, and that PCNA as well as TPO could be used to determine the growth potential of follicular proliferations in fine-needle aspirates. The most discriminant parameter was the ratio between the percentage of Mab-47 and PCNA positive cells. Ratios under 0.6 were correlated with malignancy in 90% of the cases, with only 3 cases of atypical adenomas being misdiagnosed as carcinomas. An inverse correlation was found between TPO and PCNA expression, but TG, which persisted at high levels in several actively growing follicular carcinomas, did not appear directly linked to cellular proliferation. These findings confirm that, unlike a decrease in TG synthesis that merely reflects the progressive loss of differentiation occurring in high-grade proliferations, alteration of TPO is an early marker of thyroid follicular tumors, closely related to acceleration of tumor growth in the first stages of malignant transformation.

Adenocarcinoma, Follicular↗
PubMed1998

Immunoexpression of E-cadherin and beta-catenin correlates to survival of patients with hepatocellular carcinomas.

Expression of E-cadherin (E-cad) and -catenin ( -cat) was investigated immunohistologically in 91 cases of excised hepatocellular carcinomas. Immunodectection was altered in 56% of tumours for E-cad and in 30.8% for -cat. Downregulation of E-cad and -cat correlated with the size of tumours, and high nuclear grade, but only E-cad alteration correlated with the mitotic index. Alterations of E-cad and -cat expression correlated with survival. Although E-cad and -cat immunodetections were independent prognostic factors, their prognostic value was lower than that of current clinicopathological parameters.

Adult↗
PubMed1998

[Polycystic disease of the salivary glands: report of an attack of the submaxillary glands].

Bilateral dysgenetic polycystic disease of parotid glands is an extremely rare pathologic condition in which salivary parenchyma is partially replaced by multiple epithelial-lined cysts arising from intercalated ducts. Review of the fourteen cases published in literature shows that it affects nearly exclusively women with an history of asymptomatic progressive enlargement of almost always both parotid glands. We report here the first case, to our knowledge, of a polycystic disease involving both submandibular salivary gland in a man.

Cysts↗
PubMed1998

[Prognostic value of E-cadherin expression in hepatocellular carcinoma].

Expression of E-cadherin (E-cad) was investigated immunohistologically in 91 cases of operated hepatocellular carcinomas. An alteration of E-cad immunodetection was found in 56% of tumours. These alterations were correlated with histopathologic features of prognostic value including tumour size (> 3 cm), high nuclear grade and mitotic index. Patients with down-regulated E-cad expression had statistically significant shorter survival than the others. Although E-cad immunodetection was an independent prognostic factor, the Cox multivariate analysis showed that its prognostic value was low when compared to other prognostic factors.

Adult↗
PubMed1996

Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I.

One hundred pancreatic tumors ranging in size from 0.3 to 7 cm were studied in 28 patients (17 male and 11 female patients; mean age 35 years) with multiple endocrine neoplasia, type I. An immunohistochemical study was performed on deparaffinized sections using the following antibodies: neuron-specific enolase, chromogranin A or synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, adrenocorticotropic hormone, alpha-subunit of human chorionic gonadotropin, gonadotropin-releasing factor, serotonin, and calcitonin. Among the 100 tumors (all multiple), seven were unclassified, 10 were plurihormonal, and 83 produced a predominant hormonal secretion (with 50-90% of the same cell type), including 37 "A-cell tumors" (glucagon), 27 "B-cell tumors" (insulin), 11 PP-cell tumors, one G-cell tumor (gastrin) and one vasoactive intestinal peptide (VIP)-cell tumor. These multiple tumors had a different predominant hormonal secretion in the same patient in 23 of the 28 cases. There was a preferential association of A-cell tumor and B-cell tumor. Hyperplasia of the islets of Langerhans was not detected in adjacent pancreas. Nesidioblastosis was observed in 30% of cases.

Adolescent↗
PubMed1996

[Tumor markers in the cytodiagnosis of thyroid nodules. Detection of dipeptidyl aminopeptidase IV (DAP IV) activity].

Dipeptidyl-aminopeptidase IV (DAP IV), an exopeptidase involved in T-cell activation is absent from normal thyroid tissue but highly expressed by malignant thyroid cells. It has been suggested to be a useful adjunct for the diagnosis of malignant thyroid tumors on fine needle aspirates (FNA). To assess this assumption DAP IV activity was demonstrated by histochemical staining on FNA performed on 102 thyroid nodules at the time of surgery (60 macrofollicular adenomas, 15 microfollicular adenomas. 7 Hashimoto's thyroïditis, 3 Graves' disease. 13 papillary carcinomas and 4 follicular carcinomas). A staining score based on the percentage of positive epithelial cells and staining intensity was established for each case and results were compared to histological diagnosis. Most cells in malignant tumors were deeply stained except in one case of papillary carcinoma. Null or very low scores resulting from light or medium staining of less than 40% of the cells were obtained in 78/85 benign nodules. In 6 macrofollicular adenomas and in 1 case of thyroiditis staining score was as as high as in carcinomas. DAP IV staining was correlated to malignancy in all follicular tumours (4 malignant tumours were positive and 15 benign were negative). The sensitivity for diagnosis of malignancy was 94.1% and the specificity 91.7%. This study brings confirmation that DAP IV activity detection could be an useful adjunct to cytological examination for the distinction between benign and malignant thyroid nodules, especially in cases of follicular tumors.

Biomarkers, Tumor↗