I B Rosen

University of Toronto, Toronto, Ontario, Canada

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Publications (90)306.46 Total impact

  • Julio C Furlan · Yvan C Bedard · Irving B Rosen
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    ABSTRACT: This study examines the influence of tumor capsular invasion on the biological behavior of papillary (PTC) and follicular thyroid carcinoma (FTC) and the prognosis of surgically treated patients. This retrospective cohort study included 350 cases of PTC or FTC from a university teaching hospital. Patient charts were randomly selected and reviewed. The study population was divided into PTC and FTC groups. Each group was subdivided into CI+ (with tumor capsular invasion) and CI- subgroups (without tumor capsule or without capsular invasion). The long-term prognosis was assessed using the American Joint Committee on Cancer pTNM staging and the prognostic index was elaborated by the European Organization for Research and Treatment of Cancer. There were 284 women and 66 men (ages 19-89 years, mean of 44) with an incidence of 53.1 per cent for CI+ tumors. There were no significant differences between the PTC subgroups regarding the short-term clinical outcome and the long-term prognosis. Although patients with CI+ FTC showed lower incidence of lymph node metastasis than patients with CI- FTC, the FTC subgroups were comparable regarding the short-term clinical outcome and the long-term prognosis. Our results suggest that presence of tumor capsular invasion does not adversely influence biological behavior or survival of PTC or FTC. Moreover, the presence of tumor capsular invasion appears to not have significance for the long-term prognosis of patients with PTC or FTC.
    The American surgeon 06/2007; 73(5):484-91. · 0.92 Impact Factor
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    Irving B Rosen
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    ABSTRACT: There is no significant biography that records the accomplishments of Sir Wilfred Trotter, who was a general surgeon in its pure sense at a time when surgical specialization was in its infancy. Trotter was born in the 1870s in England. Despite being bedridden during his childhood with a musculoskeletal condition he was able to study medicine at London University, and eventually became Professor and Chair of Surgery at the University College Hospital, a position he held until his death in November 1939. He made many contributions to surgical care, particularly in the field of oncology. He attended to many famous people, including King George V and Sigmund Freud and was greatly honoured in his own milieu. He was named honorary surgeon and Sargent Surgeon to the king. In addition, he was a thoughtful individual who addressed problems in human behaviour, contradicting the stereotype of the contemporary surgeon.
    Canadian journal of surgery. Journal canadien de chirurgie 09/2006; 49(4):278-80. · 1.27 Impact Factor
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    Julio C Furlan · Yvan C Bedard · Irving B Rosen
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    ABSTRACT: Fine-needle aspiration biopsy (FNAB) is considered a safe, reliable and cost-effective means of selecting thyroid nodules with risk for malignancy. However, there are limitations of this method including false positive/negative and "nondiagnostic" results that may be reduced by repeating FNAB. To evaluate accuracy, sensitivity, specificity and costs of sequential FNAB in the management of thyroid nodular disease. Charts of all patients who underwent thyroidectomy at a university teaching hospital in Toronto from 1998 to 2000 were reviewed. FNAB reports of "suspicious for malignancy," "follicular lesion" and "cellular atypia" were considered to be positive. Data were analyzed with chi2 and z tests. There were 268 patients (225 women and 43 men; age range 18-89 yr; mean age 47 yr) who underwent a total of 449 FNABs (mean 1.7 FNABs/patient) within a year before thyroidectomy. Accuracy (63.8%), sensitivity (73.8%) and specificity (69%) were determined for single FNABs. Sequential FNAB increased the accuracy of method by 22.6%, sensitivity by 13.8% and specificity by 6.2%, with reduction of false positive/negative results by 14.2% and "nondiagnostic" results by 100%. However, the costs of sequential cytology per patient were 70% higher than single FNAB. Multiple FNABs are unpleasant for patients, but useful in the selection for treatment of patients with thyroid nodular diseases. Although sequential FNAB increases the costs of method, the improvement of precision of FNAB may imply a reduction in overall health-care costs.
    Canadian journal of surgery. Journal canadien de chirurgie 03/2005; 48(1):12-8. · 1.27 Impact Factor
  • Julio C Furlan · Yvan C Bedard · Irving B Rosen
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    ABSTRACT: Since fine-needle aspiration biopsy (FNAB) was introduced, the value of frozen section (FS) has been questioned. This study compares FNAB and FS sensitivities among the usual form of papillary thyroid cancer (uPTC) and variants of PTC such as tall cell (tcPTC), follicular (fPTC), and Hurthle cell (HcPTC). A total of 257 patients who underwent preoperative FNAB, intraoperative FS, and thyroidectomy for PTC were, randomly selected from a database of a university teaching hospital in Toronto. There were 218 females (84.8%) and 39 males (15.2%), from 19 to 89 years of age (mean of 44 years), having uPTC (n = 212), fPTC (n = 24), HcPTC (n = 14), and tcPTC (n = 7). Data were analyzed using chi2 test. Sensitivities were calculated by division of true positives and by the sum of true positives and false negatives. True positives had to reflect a conclusive diagnosis of cancer. The FNAB sensitivities were uPTC (39.2%), fPTC (25%), HcPTC (42.9%), tcPTC (85.7%), similar to FS sensitivities (p = 0.497) for uPTC (44.3%), fPTC (16.7%), HcPTC (42.9%), and tcPTC (71.4%). Use of FS following FNAB increased sensitivities for uPTC to 56.1%, fPTC to 29.2%, and tcPTC to 100%. In addition, FS did not increase FNAB sensitivity in HcPTC. Combination FNAB plus FS failed in 43.9% of uPTC, 70.8% of fPTC, and 57.1% of HcPTC. We concluded that FNAB and FS sensitivity vary with PTC subtype and are still necessary for selection and treatment. The recognition of morphologic subtypes of PTC from the FNAB could optimize the selection of patients for intraoperative FS, enhance the preoperative assessment of prognosis, facilitate the surgical planning, and simplify the preparation of postoperative adjuvant therapy.
    World Journal of Surgery 10/2004; 28(9):880-5. DOI:10.1007/s00268-004-6953-z · 2.35 Impact Factor
  • Julio C Furlan · Irving B Rosen
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    ABSTRACT: Although exposure to ionizing radiation is a well-known risk factor for well-differentiated thyroid cancer, its effects on tumor behavior remain unclear. This study was undertaken to address this question. We randomly selected 426 patients who underwent thyroidectomy for cancer between 1964 and 2000 and divided them into two groups: previously exposed (ExR); not exposed to radiation (nExR). Data were retrospectively collected. There were 340 female patients and 86 male, age 9-89 years with mean follow-up of 56 months. The ExR group (n=68) was smaller than the nExR group (n=358). Most patients in the ExR group (64.5%) had previously received therapeutic radiation, whereas 25% were occupationally exposed and 10.5% were at risk from environmental radiation. Both groups were similar with regard to extent of thyroidectomy and adjuvant treatment, but neck dissections were more frequent in the nExR group. There were no significant differences between both groups for age, gender, tumor multicentricity, frequency of microcarcinoma, histology, lymph node disease, distant metastasis, and local recurrence. Incidental microcarcinomas were more frequent in the ExR (35.3%) group than in the nExR group (22.1%). Mean tumor size in the ExR group (18.7 mm) was smaller than in the nExR group (22.3 mm). Ionizing radiation increases risk for well-differentiated thyroid cancer (WDTC) but not adverse cancer behavior. Surgeons should be aware of the high incidence of microcancer among patients with previous exposure to radiation.
    Langenbeck s Archives of Surgery 07/2004; 389(3):198-203. DOI:10.1007/s00423-003-0424-0 · 2.16 Impact Factor
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    Julio C Furlan · Yvan C Bedard · Irving B Rosen
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    ABSTRACT: The association of angioinvasion with tumor aggressiveness in follicular and papillary thyroid carcinoma remains unclear. This study addresses this problem focusing on clinicopathologic relevance of angioinvasion in the treatment of papillary thyroid carcinoma and follicular thyroid carcinoma. From a university hospital database, 358 patients with papillary thyroid carcinoma or follicular thyroid carcinoma were randomly selected. Their charts were retrospectively analyzed and divided into papillary thyroid carcinoma and follicular thyroid carcinoma groups. Each group was subdivided into angioinvasive and nonangioinvasive tumor subgroups. All data were analyzed using Student's t-test, Mann-Whitney rank sum test, chi-square test, and Fisher's exact test. There were 289 women and 69 men, ages 18 to 89 years. Papillary thyroid carcinoma (86%) was more frequent than follicular thyroid carcinoma. Most patients had nonangioinvasive tumor (90.2%). After a mean followup of 43.6 months, there were no significant differences between papillary thyroid carcinoma subgroups for local recurrence (p = 0.69), persistent elevated serum thyroglobulin (p = 0.568), and distant metastasis rates (p = 0.422). No death related to the cancer was observed in both papillary thyroid carcinoma subgroups (p = 1), except for one death resulting from a concomitant nasopharyngeal cancer. The longterm prognosis was less favorable for angioinvasive papillary thyroid carcinoma based on AJCC (American Joint Committee on Cancer staging), AMES (age, distant metastasis, tumor extent, and size), and MACIS (distant metastasis, age, completeness of primary tumor resection, local invasion, and tumor size), but the angioinvasive papillary thyroid carcinoma were larger than nonangioinvasive papillary thyroid carcinomas. The short-term clinical outcomes in both follicular thyroid carcinoma, after a mean followup of 72.3 months, were comparable in terms of local recurrence (p = 0.34), persistent elevated serum thyroglobulin (p = 1), and distant metastasis (p = 0.597). There was no death related to cancer in both follicular thyroid carcinoma subgroups (p = 1). There were no significant differences between both follicular thyroid carcinoma subgroups for longterm prognosis. Our results indicate that angioinvasion does not adversely influence short-term outcomes or longterm prognosis in follicular thyroid carcinoma and short-term outcomes in papillary thyroid carcinoma. Angioinvasion is a postoperative pathologic finding that does not justify an ominous prognosis or drastic therapeutic measures.
    Journal of the American College of Surgeons 04/2004; 198(3):341-8. DOI:10.1016/j.jamcollsurg.2003.11.012 · 4.45 Impact Factor
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    ABSTRACT: This study reviewed the accuracy of fine-needle aspiration biopsy (FNAB) and the efficacy of thyroid suppression for colloid nodules in our population to determine the utility of these two modalities on the decision to operate. A retrospective chart review of patients with colloid nodules diagnosed by FNAB from January 1993 to July 1995 was conducted. A 52-patient cohort underwent surgical management, and their needle aspirate cytologies and final pathologies were reviewed. A 7.7% false-negative rate in the detection of thyroid malignancy by FNAB was obtained. This is in keeping with data reported in the literature. Virtually no efficacy of hormonal suppression in our population was found. When the literature is reviewed and compared with the results of this study, the use of FNAB as a decision tool to operate is valid. The decision to operate based on the outcome of hormonal suppression, however, is not valid based on our results.
    The Journal of otolaryngology 03/2004; 33(1):1-4. DOI:10.2310/7070.2004.02090 · 0.50 Impact Factor
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    ABSTRACT: Parotid neoplasms represent a diverse group of tumours found in the head and neck. Complications following parotidectomy, including Frey's syndrome, facial nerve paralysis, sialoceles, and parotid fistulae, have been well documented. A retrospective review of 255 patients treated surgically for parotid masses over an 8-year period at Mount Sinai Hospital in Toronto was reviewed as part of a quality assurance program. The sensitivity, specificity, and predictive values for fine-needle aspiration cytology were analyzed. The incidence of benign and malignant lesions is presented. The complications following parotidectomy are reviewed and in our series are consistent with the figures published in the literature.
    The Journal of otolaryngology 01/2003; 31(6):351-4. DOI:10.2310/7070.2002.34394 · 0.50 Impact Factor
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    Maurine R Hobbs · Irving B Rosen · Charles E Jackson
    The American Journal of Human Genetics 06/2002; 70(5):1376-7. DOI:10.1086/340093 · 10.99 Impact Factor
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    ABSTRACT: Since ret/PTC gene rearrangements are specific to papillary thyroid carcinoma (PTC), the diagnosis of Hürthle cell PTC (HCPTC) has recently been expanded to include a subset of Hürthle cell tumors (HCTs) that may lack both papillary architecture and/or classic nuclear features but that harbor a ret/PTC gene rearrangement. We hypothesize that such HCPTCs behave in a fashion analogous to other papillary carcinomas, while Hürthle cell carcinomas (HCCs) behave similarly to follicular carcinomas. At the conclusion of this article, participants should be able to discuss HCTs and to identify HCPTCS using molecular techniques. A retrospective chart review was carried out on 56 patients with HCTs. All pathological specimens were analyzed for ret/PTC gene rearrangements. Hürthle cell adenoma (HCA) was defined as an HCT that did not exhibit capsular and/or vascular invasion and that lacked a ret/PTC gene rearrangement when evaluated by immunohistochemical and reverse transcription polymerase chain reaction analysis. An HCC was defined as an HCT with capsular and/or vascular invasion that lacked a ret/PTC gene rearrangement, and an HCPTC was defined as any HCT that harbored a ret/PTC gene rearrangement. The subclassification of the 56 HCTs was as follows: 21 HCAs, 15 HCCs, and 20 HCPTCs. No patients with HCA or HCC were ret/PTC positive. Five of the 6 patients with definite lymph node metastasis were in the HCPTC group, demonstrating that molecular analysis helps to explain biological behavior. Hürthle cell neoplasms can now be classified using histopathological as well as molecular criteria. It appears that the new subclassification of malignant HCTs into follicular (HCC) and papillary (HCPTC) variants identifies 2 distinct biological groups.
    Archives of Otolaryngology - Head and Neck Surgery 04/2002; 128(3):237-40. · 1.75 Impact Factor
  • Archives of Otolaryngology - Head and Neck Surgery 03/2002; 128(3):237. DOI:10.1001/archotol.128.3.237 · 1.75 Impact Factor
  • Julio C. Furlan · Yvan Bedard · Irving B. Rosen
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    ABSTRACT: Management of thyroid microcancer or occult well-differentiated thyroid cancer (OWDTC) is controversial. Our present study compared some clinical features of OWDTC and gross well-differentiated 10-mm thyroid carcinoma (GWDTC), which may offer a basis for treatment policy. From 1964 to 2000, 1000 patients underwent thyroidectomy for thyroid cancer. We randomly selected 428 cases for study in which node sampling was carried out in 88% of GWDTC and 60% of OWDTC and who were demographically comparable. All data were obtained by chart review and analyzed by chi-square test. With the maximum limit of 10 mm for defining OWDTC, we found 113 such cases with a mean size of 6.1 mm and 315 GWDTC cases with a mean size of 27.6 mm. The incidence of metastatic nodal disease was 16.8% in OWDTC cases and 25.7% in GWDTC cases (P = .057). Distant metastases occurred in 1 of 113 (0.9%) cases of OWDTC and 11 of 315 (3.5%) cases of GWDTC (P = .149). After a mean follow-up time of 55.8 months, neck metastatic recurrent disease occurred in 3 of 113 (2.7%) cases of OWDTC and 7 of 315 (2.2%) cases of GWDTC (P = .770). OWDTC was found in 11.1% of the GWDTC group undergoing an operation. Multicentricity occurred in 31.9% of OWDTC cases and 35.9% of GWDTC cases (P = .447). No cause-specific death occurred. One cannot be dogmatic in treatment of microcancer, but one is justified in extending similar treatment principles for OWDTC as in GWDTC, which in our center usually indicates near-total thyroidectomy and consideration for radioactive iodine ablation.
    Surgery 01/2002; 130(6):1050-4. DOI:10.1067/msy.2001.118389 · 3.11 Impact Factor
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    ABSTRACT: In thyroid, the diagnosis of papillary carcinoma (PC) is based on nuclear features; however, identification of these features is inconsistent and controversial. Proposed markers of PC include HBME-1, specific cytokeratins (CK) such as CK19, and ret, the latter reflecting a ret/PTC rearrangement. We applied immunohistochemical stains to determine the diagnostic accuracy of these three markers. Formalin-fixed, paraffin-embedded tissue from 232 surgically resected thyroid nodules included 40 hyperplastic nodules (NH), 35 follicular adenomas (FA), 138 papillary carcinomas (PC; 54 classical papillary tumors and 84 follicular variant papillary carcinomas [FVPC]), 4 follicular carcinomas (FC), 6 insular carcinomas (IC), 7 Hürthle cell carcinomas (HCC), and 2 anaplastic carcinomas (AC). HBME-1 and ret were negative in all NH and FA; some of these exhibited focal CK19 reactivity in areas of degeneration. Half of the FC and AC exhibited HBME-1 staining but no positivity for CK19 or ret. In PC, 20% of cases stained for all three markers. Classical PC had the highest positivity with staining for HBME-1 in 70%, CK19 in 80%, and ret in 78%. FVPC were positive for HBME-1 in 45%, for CK19 in 57%, and for ret in 63%; only 7 FVPC were negative for all three markers. The six IC exhibited 67% staining for HBME-1 and 50% positivity for CK19 and ret. The seven HCC had 29% positivity for HBME-1 and CK19, and 57% positivity for ret. This panel of three immunohistochemical markers provides a useful means of diagnosing PC. Focal CK19 staining may be found in benign lesions, but diffuse positivity is characteristic of PC. HBME-1 positivity indicates malignancy but not papillary differentiation. Only rarely are all three markers negative in PC; this panel therefore provides an objective and reproducible tool for the analysis of difficult thyroid nodules.
    Modern Pathology 05/2001; 14(4):338-42. DOI:10.1038/modpathol.3880312 · 6.36 Impact Factor
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    ABSTRACT: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease characterized by the development of multiple parathyroid adenomas and multiple fibro-osseous tumors of the maxilla and mandible. Some families have had affected members with involvement of the kidneys, variously reported as Wilms tumors, nephroblastomas, and hamartomas. The HPT-JT gene (HRPT2) maps to chromosome 1q25-q31. We describe further investigation of two HPT-JT families (K3304 and K3349) identified through the literature. These two expanded families and two previously reported families were investigated jointly for linkage with 21 new, closely linked markers. Multipoint linkage analysis resulted in a maximum LOD score of 7.83 (at recombination fraction 0) for markers D1S2848-D1S191. Recombination events in these families reduced the HRPT2 region to approximately 14.7 cM. In addition, two of these four study families (i.e., K3304 and K11687) share a 2.2-cM length of their (expanded) affected haplotype, indicating a possible common origin. Combining the linkage data and shared-haplotype data, we propose a 0.7-cM candidate region for HRPT2.
    The American Journal of Human Genetics 03/1999; 64(2):518-25. DOI:10.1086/302259 · 10.99 Impact Factor
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    ABSTRACT: Background. Our purpose was to study the expression of multiple oncogenes in papillary thyroid cancer for possible interactions and prognostic significance. Methods. Twenty papillary thyroid carcinomas were studied for expression/mutation of 3 oncogenes: ras, ret/PTC, and erbB- 2/neu. H, N, and K ras codons were examined by polymerase chain reaction (PCR), single-stranded conformation polymorphism, and sequencing. The thyroid oncogene ret/PTC was identified by reverse transcription (RT)-PCR. Gene amplification of erbB-2/neu was analyzed by differential PCR. The transmembrane domain of erbB-2/neu was sequenced for activating mutations. Quantitation of erbB-2/neu mRNA was evaluated by competitive RT-PCR, and protein expression was determined by immunohistochemistry. Results. Among 20 tumors, 3 had insular/anaplastic dedifferentiation, 13 were intrathyroidal, and 7 were metastatic to cervical lymph nodes (6) or lung (1). An H-ras 13 mutation was found in 1 metastatic tumor and an N-ras 61 mutation in 1 intrathyroidal tumor. ret/PTC was identified in 3 intrathyroidal and 5 metastatic tumors. No erbB-2/neu DNA amplification or mutations were identified, although 4 tumors had elevated erbB-2/neu mRNA levels. Three of 20 patients had abnormalities detected in multiple oncogenes; 2 had elevated erbB-2/neu mRNA and ret/PTC rearrangements, and 1 of these had pulmonary metastasis. An intrathyroidal papillary cancer had an N61 ras mutation and a ret/PTC gene rearrangement. Conclusions. ret/PTC rearrangements are present in 40 % of papillary thyroid carcinomas and may play a role in metastatic behavior. In contrast, ras mutations are rare (10%). erbB-2/neu gene amplify- cation and activating mutations are not detected, although elevated mRNA levels were found in 20 % of papillary carcinomas. The lack of correlation among the 3 oncogenes in 17 of 20 (85%) papillary thyroid carcinomas suggests that they were not cumulative factors in the pathogenesis of these tumors.
    Surgery 02/1999; 125(1-125):46-52. DOI:10.1016/S0039-6060(99)70287-4 · 3.11 Impact Factor
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    ABSTRACT: Amplification and overexpression of the erbB-2 proto-oncogene in human carcinomas may have prognostic significance. Its role in thyroid carcinoma is controversial. We investigated human thyroid tumours for erbB-2 gene amplification, activating mutations in the transmembrane domain, quantitative mRNA expression and protein expression. DNA and mRNA were extracted from 47 morphologically characterized, frozen thyroid tumours including 10 nodular hyperplasias, 3 follicular carcinomas and 34 papillary carcinomas (4 with tall-cell features, 2 with insular and 2 with anaplastic de-differentiation). DNA amplification was analysed by differential PCR. The transmembrane domain of erbB-2 was sequenced in all tumours for activating mutations in position 659. Levels of mRNA expression were determined by competitive mRNA RT-PCR. Immunohistochemistry (IHC) for erbB-2 protein expression in corresponding paraffin-embedded samples was evaluated. Our results showed no DNA amplification of erbB-2. Sequencing of the transmembrane domain of erbB-2 revealed no activating mutations. The level of mRNA expression was variable, 11 papillary carcinomas showing statistically significant elevated mRNA levels compared with corresponding normal thyroid tissue; however, this did not correlate with other indicators of poor prognosis. In contrast to elevated mRNA levels in tumours, the level of protein staining correlated with degree of differentiation, normal and hyperplastic tissue being strongly positive and poorly differentiated tumours negative. There are no mutations or amplifications of the erbB-2 gene in human thyroid tumours. Elevated erbB-2 mRNA expression in some thyroid tumours is not associated with clinical features of poor prognosis; however, the significance of the elevated mRNA levels is unclear, as it did not result in protein overexpression. Instead, cytoplasmic erbB-2 protein detection by IHC correlates with differentiation of human thyroid tumours and may be a feature of good prognosis.
    Clinical Endocrinology 12/1998; 49(5):629-37. DOI:10.1046/j.1365-2265.1998.00580.x · 3.35 Impact Factor
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    S L Sugg · S Ezzat · I B Rosen · J L Freeman · S L Asa
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    ABSTRACT: Rearrangements involving the RET protooncogene have been implicated in the development of papillary thyroid carcinoma (PC). Transgenic mice, expressing thyroid-targeted RET/PTC-1, develop PC; but the clinical significance of this oncogene remains uncertain. We examined the expression of RET/PTC-1, -2, and -3 in human thyroid microcarcinomas and clinically evident PC to determine its role in early stage vs. developed PC and to examine the diversity of RET/PTC in multifocal disease. RNA was extracted from paraffin-embedded microcarcinomas and clinically evident PCs; the results obtained from paraffin-embedded tissue were confirmed on RNA from corresponding snap-frozen tissue of clinically evident PCs. RT and PCR was performed using primers for RET/PTC-1, -2, and -3; PGK-1 (the housekeeping gene) analysis was used to ensure integrity of the RNA and efficiency of the RT reaction. PCR products were resolved by gel electrophoresis, and Southern hybridization was performed with RET/PTC-1, -2, and -3 probes. A polyclonal antibody to the carboxyterminus of RET was used for immunohistochemistry on paraffin sections. Thirty-nine occult papillary thyroid microcarcinomas from 21 patients were analyzed. Of the 30 tumors (77%) positive for RET/PTC rearrangements, 12 were positive for RET/PTC-1, 3 for RET/ PTC-2, 6 for RET/PTC-3, and 9 for multiple RET/PTC oncogenes. In clinically evident tumors, 47% had RET/PTC rearrangements. Immunohistochemistry demonstrated close correlation with RT-PCR-derived findings. RET/PTC expression is highly prevalent in microcarcinoma and occurs more frequently than in clinically evident PC (P < 0.005). Multifocal disease, identified in 17 of the 21 patients, exhibited identical RET/PTC rearrangements within multiple tumors in only 2 patients; the other 15 patients had diverse rearrangements in individual tumors. Our results indicate that RET/PTC oncogene rearrangements may play a role in early-stage papillary thyroid carcinogenesis, but they seem to be less important in determining progression to clinically-evident disease. In multifocal disease, the diversity of RET/PTC profiles, in the majority of cases, suggests that individual tumors arise independently in a background of genetic or environmental susceptibility.
    Journal of Clinical Endocrinology &amp Metabolism 12/1998; 83(11):4116-22. · 6.31 Impact Factor
  • IRVING B. ROSEN · MARK KORMAN · PAUL G. WALFISH
    Clinical Obstetrics and Gynecology 04/1997; 40(1):81-9. DOI:10.1097/00003081-199703000-00009 · 1.53 Impact Factor
  • Irving B. Rosen · Mark Korman
    Bulletin of anesthesia history 04/1997; 15(2):11-13. DOI:10.1016/S1522-8649(97)50028-X
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    ABSTRACT: Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only S of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extra thyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.
    Endocrine Pathology 02/1997; 8(1):21-28. DOI:10.1007/BF02739704 · 1.64 Impact Factor

Publication Stats

3k Citations
306.46 Total Impact Points

Institutions

  • 1975–2007
    • University of Toronto
      • • Department of Surgery
      • • Department of Laboratory Medicine and Pathobiology
      • • Mount Sinai Hospital
      Toronto, Ontario, Canada
  • 1974–2002
    • Mount Sinai Hospital, Toronto
      • Department of Otolaryngology
      Toronto, Ontario, Canada
  • 1993
    • MetroHealth Medical Center
      Cleveland, Ohio, United States
  • 1990–1992
    • Mount Sinai Hospital
      New York City, New York, United States
  • 1986–1989
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada