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Pathological Characteristics (pathological + characteristic)
Selected AbstractsThe role of tau (MAPT) in frontotemporal dementia and related tauopathies,HUMAN MUTATION, Issue 4 2004R. Rademakers Abstract Tau is a multifunctional protein that was originally identified as a microtubule-associated protein. In patients diagnosed with frontotemporal dementia and parkinsonism linked to chromosome 17, mutations in the gene encoding tau (MAPT) have been identified that disrupt the normal binding of tau to tubulin resulting in pathological deposits of hyperphosphorylated tau. Abnormal filamentous tau deposits have been reported as a pathological characteristic in several other neurodegenerative diseases, including frontotemporal dementia, Pick Disease, Alzheimer disease, argyrophilic grain disease, progressive supranuclear palsy, and corticobasal degeneration. In the last five years, extensive research has identified 34 different pathogenic MAPT mutations in 101 families worldwide. In vitro, cell-free and transfected cell studies have provided valuable information on tau dysfunction and transgenic mice carrying human MAPT mutations are being generated to study the influence of MAPT mutations in vivo. This mutation update describes the considerable differences in clinical and pathological presentation of patients with MAPT mutations and summarizes the effect of the different mutations on tau functioning. In addition, the role of tau as a genetic susceptibility factor is discussed, together with the genetic evidence for additional causal genes for tau-positive as well as tau-negative dementia. Hum Mutat 24:277,295, 2004. © 2004 Wiley-Liss, Inc. [source] Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal-like phenotype and poor prognosisHISTOPATHOLOGY, Issue 2 2010Lin Yu Yu L, Yang W, Cai X, Shi D, Fan Y & Lu H (2010) Histopathology,57, 193,201 Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal-like phenotype and poor prognosis Aims:, To investigate the clinicopathological features and immunophenotype of centrally necrotizing carcinoma (CNC) of the breast to ascertain its relationship to basal-like phenotype and its prognosis. Methods and results:, The clinical and pathological characteristics of 33 CNCs were reviewed. Immunohis-tochemical study of oestrogen receptor, progesterone receptor, HER2, cytokeratin (CK) 8/18, high-molecular-weight CK (34,E12), CK5/6, CK14, CK17, smooth muscle antigen, p63, vimentin and epidermal growth factor receptor was performed. The striking feature of CNC was a central, necrotic or acellular zone surrounded by a ring-like area of viable tumour cells. The central zone showed three morphological types: predominance of coagulative necrosis (21 cases), predominance of fibrosis and scar tissue (nine cases) and infarction (three cases). Tumour cells displayed invasive ductal carcinoma of high grade. The expression rate of basal-like markers was higher than that of myoepithelial markers (87.9% versus 46.2%). Basal-like subtype was shown by 63.6% of cases. The expression rate of CK5/6 (90.5%) was highest among basal-like markers. Follow-up data of 19 patients were available. Median progression-free survival was 15.5 months. In 12 patients (63.2%), local recurrence and/or distant metastasis developed (median time to recurrence and/or metastasis, 14.0 months). Conclusions:, CNC has distinctive morphological features, which mostly exhibit a basal-like immunophenotype and poor prognosis. CNC is a typical representative of basal-like breast cancer. [source] Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial-type pharyngeal squamous cell carcinomaHISTOPATHOLOGY, Issue 4 2010Satoshi Fujii Fujii S, Yamazaki M, Muto M & Ochiai A (2010) Histopathology56, 510,522 Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial-type pharyngeal squamous cell carcinoma Aims:, Superficial squamous epithelial lesions of the pharynx are increasingly recognized by architectural changes in the intraepithelial papillary capillary loop (IPCL) assessed by narrow-band imaging (NBI). The aim was to explore the histology of squamous epithelial precursor lesions and superficial-type pharyngeal squamous cell carcinoma (STPSCC), including squamous cell carcinoma (SCC) in situ and early invasive SCC, by focusing on microvascular irregularities to investigate the composition of those lesions and to explore the pathological characteristics of STPSCCs. Methods and results:, Several pathological factors including thickness of intraepithelial squamous cell carcinoma (IESCC) and tumour thickness and microvascular density (MVD) were examined in 104 STPSCCs from 69 patients. The results show that architectural change of IPCL was recognized in precursor lesions in parallel with architectural disturbance and cytological atypia for criteria of diagnosing dysplasia. In 104 STPSCCs, the MVD of IESCC was correlated with the thickness of IESCC (P = 0.0115). Moreover, invasive SCC showed significantly higher MVD of IESCC (P = 0.0078) and there was significant correlation between the thickness of IESCC and subepithelial invasion (P < 0.0001). Conclusions:, Microvascular irregularities are an important pathological factor in carcinogenesis and early invasiveness of SCC of the pharynx. [source] Assessment of the three-dimensional relationship of the ossific nuclei and cartilaginous anlagen in congenital clubfoot by 3-D MRIJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005Tomonobu Itohara Abstract Purpose: Radiographic measurement is the usual method used to objectively determine the extent of a congenital clubfoot deformity. Although radiographs have been used clinically to estimate the size and location of tarsal bones through measurements of the ossific nuclei, it is not clear to what extent these relationships are actually reflected in these measurements. So, we used a 3-D MRI system that could more objectively estimate sizes and positional relationships. Material and method: We evaluated 5 patients with unilateral congenital clubfoot deformity. Magnetic resonance imaging was performed of both feet using 1.5-T magnet. Based on the resulting magnetic resonance imaging volume data, a three-dimensional surface bone model was reconstructed by the Marching Cubes method. We used this model to perform a comparative analysis of the volume and volume ratio of each cartilaginous anlage and ossific nucleus, the length of the talus and the calcaneus, and the position of the center of gravity of ossific nuclei within the cartilaginous anlagen. We measured the relationship between the ossific nuclei and cartilaginous anlagen in the talus and calcaneus of patients with unilateral clubfoot deformity. Result: In clubfeet talus volume was reduced by 20.1% and calcaneal volume was reduced by 15.7%. Furthermore, the volume of the talar ossific nucleus was reduced by 42.6% and that of the calcaneal ossific nucleus was reduced by 12.1%. The length of the clubfoot talus was 8.2% shorter than normal, and that of the calcaneus was 4.8% shorter. Conclusion: The assessment technique presented herein was shown to be useful in ascertaining the various pathological characteristics associated with clubfoot. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Genetic polymorphism of CCR2-64I increased the susceptibility of hepatocellular carcinoma,JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Chao-Bin Yeh MD Abstract Background and Objectives The purpose of this study was to investigate genetic impact of monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine receptor-2 (CCR2) gene polymorphisms on the susceptibility and clinicopathological characteristics of hepatocellular carcinoma (HCC). Methods A total of 446 subjects, including 344 healthy controls and 102 patients with HCC, were recruited in this study and subjected to PCR-RFLP to estimate the impact of these two polymorphic variants on HCC. Results No relationship between MCP-1 ,2518G/A gene polymorphism and HCC risk was found among our recruited HCC patients and healthy controls. However, there was a significantly increased risk (AOR,=,1.91; 95% CI,=,1.11,3.29) of having HCC among subjects with GA heterozygotes of CCR2 V64I after adjusting for other confoundings. There was no synergistic effect between gene polymorphism and environmental risk factors, including tobacco and alcohol consumptions, as well as clinicopathological parameters of HCC for MCP-1 ,2518G/A and CCR2 V64I genes, respectively. Conclusions CCR2-64I gene polymorphism is an important factor for the susceptibility of HCC but it might not influence the clinical pathological progression of HCC, and the contribution of CCR2-64I gene polymorphism on the susceptibility of HCC could be not through the affection of liver injury-related clinical pathological characteristics. J. Surg. Oncol. 2010;102:264,270. © 2010 Wiley-Liss, Inc. [source] Insights into Serotonin Signaling Mechanisms Associated with Canine Degenerative Mitral Valve DiseaseJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010M.A. Oyama Little is known about the molecular abnormalities associated with canine degenerative mitral valve disease (DMVD). The pathology of DMVD involves the differentiation and activation of the normally quiescent mitral valvular interstitial cell (VIC) into a more active myofibroblast phenotype, which mediates many of the histological and molecular changes in affected the valve tissue. In both humans and experimental animal models, increased serotonin (5-hydroxytryptamine, 5HT) signaling can induce VIC differentiation and myxomatous valve damage. In canine DMVD, numerous lines of evidence suggest that 5HT and related molecules such as transforming growth factor-, play a critical role in the pathogenesis of this disease. A variety of investigative techniques, including gene expression, immunohistochemistry, protein blotting, and cell culture, shed light on the potential role of 5HT in the differentiation of VIC, elaboration of myxomatous extracellular matrix components, and activation of mitogen-activated protein kinase pathways. These studies help support a hypothesis that 5HT and its related pathways serve as an important stimulus in canine DMVD. This review describes the pathological characteristics of canine DMVD, the organization and role of the 5HT pathway in valve tissue, involvement of 5HT in human and experimental models of valve disease, avenues of evidence that suggest a role for 5HT in naturally occurring DMVD, and finally, a overarching hypothesis describing a potential role for 5HT in canine DMVD. [source] Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndromeMOVEMENT DISORDERS, Issue 8 2005Yoshio Tsuboi MD Abstract The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD. © 2005 Movement Disorder Society [source] Prognosis and pathological characteristics of five children with non-Shiga toxin-mediated hemolytic uremic syndromePEDIATRICS INTERNATIONAL, Issue 2 2007ICHIRO KAMIOKA Abstract Background: The three major signs of hemolytic uremic syndrome (HUS) are hemolytic anemia, thrombopenia and acute renal failure. HUS is classified into Shiga toxin-mediated HUS (Stx-HUS) and non-Shiga toxin-mediated HUS (nStx-HUS). The prognosis of nStx-HUS is reported to be less favorable than that of Stx-HUS. Although the association between the prognosis and pathological characteristics of HUS have been reported such that the prognosis was considered to be poor for thrombotic microangiopathy (TMA) with predominant arterial involvement (arterial TMA), good for TMA with predominant glomerular involvement (glomerular TMA) and dependent on the extent of necrosis in cases of renal cortical necrosis, it is not yet clear whether pathological findings are also related to the renal prognosis of nStx-HUS cases. Therefore the purpose of the present paper was to analyze renal biopsy findings and prognosis for five children with nStx-HUS. Methods: Clinical records of five cases of nStx-HUS among 74 cases of diagnosed HUS were reviewed, and information and data were summarized. Results: Histological examination of the kidney led to the diagnosis of arterial TMA in three cases, and glomerular TMA and severe renal cortical necrosis in one case each. Analysis of the relationship between renal histological findings and the prognosis found that three patients with arterial TMA and one patient with severe renal cortical necrosis later developed end-stage renal failure while one patient with glomerular TMA has continued to show normal renal function. Conclusions: These findings indicate that pathological findings are closely related to the prognosis in cases of nStx-HUS. [source] Laryngeal presentation of systemic apolipoprotein A-I,derived amyloidosis,THE LARYNGOSCOPE, Issue 3 2009Aldert J. C. Hazenberg MD Abstract Objective: To study the clinical and pathological characteristics of two patients with laryngeal apolipoprotein A-I (apoA-I)-derived (AApoAI) amyloidosis with the apolipoprotein A-I variants Leu174Ser and Leu178Pro, respectively. The latter variant has not been associated with amyloid before. Study Design: Descriptive report of two patients who presented with laryngeal amyloid presumed to be of localized AL type, but in who further assessments demonstrated systemic amyloidosis. Methods: The larynx was examined by videolaryngostroboscopy. The voice was analyzed with the GRBAS system, phonation times, and phonetography. Laryngeal biopsies were stained with Congo red and analyzed immunohistochemically. Organ function was assessed and tissue involvement by amyloid further determined by rectal biopsy, abdominal fat tissue aspirate, and serum amyloid P component scintigraphy. Results: The appearance of the laryngeal amyloid was unusual in both patients, occurring as small, irregular floppy proliferations affecting the borders of both vocal folds. Amyloid was stained with antibodies to apoA-I and not with antibodies to immunoglobulin light chains. The 45-year-old woman with the previously described amyloidogenic apoA-I Leu174Ser variant had possible involvement by amyloid in joints, peripheral nerves, and heart. Whereas in the 67-year-old man with apoA-I Leu178Pro there was a clinical suggestion of autonomic and cardiac amyloid and histological corroboration of systemic amyloidosis in abdominal fat. Conclusions: Laryngeal symptoms may be the presenting feature of hereditary systemic AApoAI amyloidosis, and comprehensive investigations including apoA-I genotyping are warranted in patients who present with apparently localized laryngeal amyloidosis. The distinctive appearance of the amyloidotic vocal folds described here may further signal the possibility of hereditary AApoAI type. Laryngoscope, 119:608,615, 2009 [source] The homozygous P582S mutation in the oxygen-dependent degradation domain of HIF-1, is associated with increased risk for prostate cancerTHE PROSTATE, Issue 1 2007Avi Orr-Urtreger Abstract BACKGROUND The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor 1), consisting of a critically regulated HIF-1, subunit and a constitutively expressed HIF-1, subunit, is a master regulator of genes involved in adaptation and survival under low-oxygen conditions. Increased levels of HIF-1 activity are associated with increased tumor aggressiveness, therapeutic resistance, and mortality. METHODS We studied 402 prostate cancer patients for the presence of the 1772C,>,T (P582S) and 1790G,>,A (A588T) mutations within the oxygen-dependent domain of HIF-1,. RESULTS Homozygosity for the P582S mutation was fourfold greater among prostate cancer patients compared to controls (OR,=,4.10 [C.I. 95% 1.11,<,OR,<,17.87], P,=,0.018). The existence of this mutation in prostate cancer patients was not associated with any of the clinical or pathological characteristics of the disease. No significant differences were found between the frequencies of A588T mutation in prostate cancer patients and controls. CONCLUSIONS Our data suggest that homozygous HIF1A P582S mutation confers significant susceptibility to prostate cancer. Prostate 67:8,13, 2007. © 2006 Wiley-Liss, Inc. [source] Clinical and pathological evaluation of patients with early and late recurrence of colorectal cancerASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Mahdi AGHILI Abstract Aim: To compare the characteristics of primary cancer between patients with early recurrence and those with late recurrence of colorectal cancer. Methods: Overall 535 patients with primary colorectal cancer were reviewed and of these 130 patients with demonstrated recurrence were evaluated. Of the 130 patients, 91 had early recurrence (less than 2 years after surgery) and 39 had late recurrence (2 years or more after surgery). The clinical and pathological characteristics of primary cancer in these two groups were compared. Results: The rate of late recurrence was 30% of total recurrences (39/130). On average, patients with early recurrence were younger than patients with late recurrence (mean age 48 vs 54 years, p = 0.027). Adjacent organ involvement and Dukes stage C was more prevalent in the early recurrence group than in the late group. The liver was the main site of distant recurrence in the early recurrence group (64% of distant recurrences), whereas bone and peritoneum were the most frequent sites of metastases in the late recurrence group (58%). In Dukes C colon cancer patients the disease-free interval was significantly longer in those who received both adjuvant therapies than in those who received either radiotherapy or chemotherapy or neither of them. Conclusion: This study showed that factors such as primary clinical signs, stage of primary tumor, and adjacent organ involvement are significant with respect to the time for recurrence of colorectal cancer. It is important to take these characteristics into account in patient care management after curative resection for colorectal cancer. [source] A delay in radical nephroureterectomy can lead to upstagingBJU INTERNATIONAL, Issue 6 2010Matthias Waldert Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To examine the association between the delay from diagnosis of upper-tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU), and the pathological features and outcomes, as the decision to proceed to RNU for an individual patient is complex. PATIENTS AND METHODS The records of 187 patients who had RNU were reviewed; the interval from diagnosis to RNU was analysed as both a continuous (months) and categorical variable (<3 vs ,3 months). Logistic regression and survival analyses were used to evaluate the association between time from diagnosis to RNU with pathological characteristics and clinical outcomes. RESULTS The median time from diagnosis to RNU was 45 days (interquartile range 68). A delay from diagnosis to RNU analysed as a continuous variable was associated with advanced stage, higher grade, previous endoscopic procedure, tumour necrosis, infiltrative tumour architecture, and lymphovascular invasion (P = 0.034), but not disease recurrence or cancer-specific mortality. In the subgroup of patients (90, 48.1%) who had muscle-invasive disease (,pT2) a longer delay from diagnosis to RNU as a continuous variable was associated with advanced stage (P = 0.030), higher grade (P = 0.014), infiltrative tumour architecture (P = 0.044), lymphovascular invasion (P = 0.034), disease recurrence (P = 0.02), and cancer-specific mortality (P = 0.03). CONCLUSIONS Our data suggest that a delay in the interval from diagnosis to RNU is associated with more advanced disease stage. These findings might have important implications for trial design in the ongoing evaluation of neoadjuvant regimens. Timely consideration of definitive treatment for patients with high-risk UTUC is of high importance. Further studies are necessary to validate these hypothesis-generating findings. [source] Changes in the stage and surgical management of renal tumours during 1995,2005: an analysis of the Dutch national histopathology registryBJU INTERNATIONAL, Issue 8 2008Intan P.E.D. Kümmerlin OBJECTIVE To evaluate changes in the pathological characteristics, stage of primary renal tumours and their surgical management in the Netherlands during the period 1995,2005. METHODS Extracts from the records of all patients who had surgery for primary renal tumours in the Netherlands during the period 1995,2005 were reviewed. Data were collected from PALGA, the nationwide network and archive of histocytopathology. The 2002 Tumour-Node-Metastasis and the three-tier Fuhrman grade were used for staging and grading. RESULTS In all there were 12 471 operations for primary renal masses during the study period. The incidence of surgically removed renal cancers increased from 6.2 in 1995 to 7.5 cases per 100 000 inhabitants (P = 0.005) in 2005. The mean (sd, median) age of the patients was 63.3 (11.9, 65.0) years, with a male-to-female ratio of 3:2. The mean (sd) tumour size of malignant tumours decreased from 7.3 (3.6) to 6.9 (3.7) cm (P = 0.301). The percentage of benign removed tumours remained relatively stable (P = 0.056), with a mean of 5.4% of all resected tumours. There was an increase of grade 1 tumours; the incidence of T1 tumours increased from 36.6% to 44.2%, and advanced tumours decreased from 46.4% to 33.7%, respectively. The percentage of nephron-sparing surgery increased from 3.5% in 1995 to 10.1% (P = 0.003) in 2005, mainly in the T1a tumours. CONCLUSIONS During the last decade there was an increase in the incidence of surgically treated renal tumours in the Netherlands. Tumours with favourable histopathological characteristics, low stage and grade, accounted for most of this increase. The percentage of surgically removed benign tumours remained stable. The use of nephron-sparing surgery increased during the last decade, especially in T1a tumours. [source] The maximum tumour length in biopsy cores as a predictor of outcome after radical prostatectomyBJU INTERNATIONAL, Issue 2 2008Norihiro Hayashi OBJECTIVES To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate-specific antigen (PSA)-failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis. RESULTS The median (range) MTL was 4 (0.2,19) mm and correlated with adverse pathological findings, including specimen Gleason score (P = 0.003), pT3 (P < 0.001), seminal vesicle invasion (P < 0.001) and lymph node involvement (P = 0.019) in multivariate analysis. Preoperative PSA (P < 0.001), biopsy Gleason score (P = 0.002), and MTL (P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic-failure (P < 0.001) and death from prostate cancer (P = 0.004). The median (range) follow-up after surgery was 90 (17,152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer. CONCLUSIONS The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies. [source] Inhibition of tumor-induced edema by antisense VEGF is mediated by suppressive vesiculo-vacuolar organelles (VVO) formationCANCER SCIENCE, Issue 12 2008Zhi Xiong Lin Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis, vasculogenesis and vascular permeability. Edema in glioma tumors is considered one of the most pathological characteristics, but the mechanism of regulating vascular permeability is still unclear. In the present study, tumorigenic mice were generated by subcutaneous injection of glioma cell lines, C6-null cells and stable transfected-C6 cells overexpressing mock vector (C6-mock) and antisense VEGF (C6-VEGF,/,). Overexpression of antisense VEGF (C6-VEGF,/, mice) significantly suppressed tumor growth, decreased angiogenesis and reduced tumoral edema. Further studies by electron microscope revealed that tumor-induced hyperpermeability was mediated by formation of vesiculo-vacuolar organelles (VVO), specifically reducing the number of vesicle and caveolae in VVO, and this effect was blocked, at least partially, by antisense VEGF. These data show a possible mechanism of tumor-induced hyperpermeability and indicate that blockage of VEGF might contribute to therapeutical strategies for tumor edema. (Cancer Sci 2008; 99: 2540,2546) [source] Association of HLA DQ4-DR8 haplotype with papillary thyroid carcinomasCLINICAL ENDOCRINOLOGY, Issue 2 2006Teresa Porto Summary Objective, The association of the human leucocyte antigen (HLA) system with thyroid carcinomas is not clear. We sought to relate HLA alleles to susceptibility to papillary thyroid carcinoma (PTC) and also to clinical and pathological characteristics of PTC patients. Design and patients, The distribution of HLA in 181 unrelated Caucasian patients with PTC was compared to the HLA distribution in 315 normal controls, 31 patients with follicular carcinoma (FTC), 29 patients with lymphocytic thyroiditis (LT) and 50 patients with multinodular goitre (MNG), using a microlymphocytotoxicity assay. Results, Compared to normal controls, patients with PTC showed a significantly increased frequency of HLA-DQ4 [12·8%vs. 3·5%, P = 0·0005, Pcorrected (Pc) = 0·0032, odds ratio (OR) = 4·058, 95% confidence interval (95% CI) = 1·820,9·045] and HLA-DR8 (10·9%vs. 4·3%, P = 0·013, Pc > 0·05, OR = 2·752, 95% CI = 1·275,5·940). DQ4 and DR8 were also significantly increased in patients with MNG (DQ4, 16·3%; DR8, 16·3%) compared to controls (DQ4, P = 0·0019, Pc = 0·011, OR = 5·420, 95% CI = 1·978,14·852; DR8, P = 0·0044, Pc = 0·062). Linkage disequilibrium (LD) for these two alleles was present in controls (D = 0·0130, P = 9·7e-57) and in MNG patients (D = 0·0730, P = 4·6e-19) but not in PTC patients (D = 0·038, P > 0·05). In the subgroup of PTC subjects with concomitant nonthyroidal neoplasias (n = 27), there was a significant (P < 0·05) increase in the frequency of B57 (18·5%), DR11 (56·5%) and DQ3 (81·8%) compared to PTC patients without coexistent neoplasias (2·0%, 21% and 47%, respectively). No significant differences of HLA allele distribution was found in relation to PTC histology, age at diagnosis (> 45 or , 45 years), gender or tumour,node,metastasis (TNM) staging. In patients with FTC, the frequency of DR17 (FTC = 51·6%; controls = 22·5%; P = 0·0009; Pc = 0·0138) was significantly increased compared to controls. Patients with LT showed a higher frequency of the DR11 allele (48·3%) than controls (DR11 = 21·3%; P = 0·0028, Pc = 0·039, OR = 3·445, 95% CI = 1·568,7·567). Conclusions, We have typed the largest series of patients with thyroid carcinomas reported to date, and found that DR8 and DQ4 are independent susceptibility markers for PTC. [source] | |||||||||||||||||||||||||