A Rare Cause of Chronic Liver Disease Diagnosed by Endoscopic Ultrasound-Guided Liver Biopsy.

BACKGROUND Elevated liver enzymes is a common clinical problem with many possible etiologies, yet some are rare and can be missed. Patients with sickle cell disease (SCD) may be at risk of liver disease due to recurrent blood transfusion predisposing to viral hepatitis. Furthermore, recurrent transfusions can increase the risk of iron overload, which can create deposits in the liver, eventually resulting in chronic liver disease. Liver biopsy is an essential tool to establish a diagnosis of liver disease in many patients with unexplained elevation of liver enzymes. Recently, endosocpic ultrasound (EUS)-guided liver biopsy has been shown to be safe and effective in obtaining adequate liver tissue. However, the safety and efficacy has not been established in patients with SCD. CASE REPORT A 59-year-old man with SCD and beta-thalassemia minor was evaluated for persistently elevated liver enzymes (mainly cholestatic). He had a background history of treated hepatitis C virus infection. He had multiple blood transfusions in the past for sickle cell crisis. A diagnostic work-up revealed negative viral and autoimmiune serology and no evidence of biliary obstruction on abdominal imaging. The iron profile was elevated, consistent with iron overload. An EUS-guided liver biopsy confirmed a diagnosis hepatic hemosiderosis secondary to long-term blood transfusions. CONCLUSIONS This report emphasizes the importance of careful monitoring of iron levels in patients with hematological conditions requiring long-term blood transfusions. In addition, it highlights the emerging role of EUS-guided liver biopsy as a safe and accurate alternative to percutaneous liver biopsy.

Vitamin D pathway related polymorphisms and vitamin D receptor expression in breast cancer.

Vitamin D deficiency is an emerging risk factor for breast cancer suggesting its role in breast cancer pathogenesis. Recent evidence suggests vitamin D receptor (VDR) expression is a prognosis predictor in breast cancer. We set out to determine the status of VDR expression in histologically characterized breast cancers, and whether common genetic variants modify VDR expression in breast cancer. One-hundred and twenty Kuwaiti female breast cancer fixed tissues were assessed for VDR expression to identify the level and location of its expression by immunohistochemistry. VDR variants (rs731236, rs2228570), and vitamin D binding protein (VDBP) variants (rs4588, rs7041) genotypes were ascertained in breast cancer specimens using Taqman genotyping assays. VDR nuclear expression correlated with low grade tumors (p = 0.01), whereas cytoplasmic expression correlated with lymph node positive tumors (p = 0.03). Absence of VDR expression was a marker for high-grade dedifferentiated tumors (p = 0.01). VDBP rs7041 associated with breast cancer risk (OR 1.92, 95% CI: 1.34 - 2.73; p = 0.0004), and VDR rs2228570 correlated with increased VDR cytoplasmic expression (p < 0.0001). In conclusion, VDR expression is altered in breast cancer confirming its involvement in breast cancer progression. Genetic factors appear to play a role in breast cancer risk, and may modify tumor sensitization to vitamin D.

Hormone Receptors and Human Epidermal Growth Factor (HER2) Expression in Fine-Needle Aspirates from Metastatic Breast Carcinoma - Role in Patient Management.

INTRODUCTION: Estrogen receptors (ER), progesterone receptors (PR), and epidermal growth factor (HER2) are prognostic and predictive factors for breast carcinoma. We determined them by immunohistochemistry (IHC) on cell blocks from fine-needle aspirates (FNA) of metastatic breast carcinoma to axillary lymphnodes and compared them with that reported in the primary breast carcinoma (PBC) to document any change in their expression for future management. MATERIALS AND METHODS: ER, PR, and HER2 by IHC and HER2 oncogene by fluorescent in-situ hybridization (FISH) were studied on cell blocks of FNA of axillary lymphnodes in 53 of 94 PBC cases from 2012 to 2016. RESULTS: In 25 of 38 (65.8%) ER, PR negative PBC the metastasis on FNA was ER, PR+, whereas the 15 (28.3%) ER, PRPBC remained negative. In 10 of 11 (91%) of HER2-IHC+, PBC the metastatic tumor was HER2-IHC+. 7 of 32 (21.9%) HER2-IHC negative PBC were HER2-IHC+ in metastatic tumor. HER2-FISH was performed in 37 cases on FNA. Six of 37 were HER2 amplified/positive, whereas 9 and 19 remained equivocal and negative for HER2 copy number, and 3 were not interpretable. All the 6 HER2-FISH+ cases were positive by IHC. In our study, 34.2% of ER, PR+ cases of PBC became ER, PR- in the metastatic tumor and 21.9% of HER2-IHC negative PBC became HER2-IHC+ in the metastatic aspirate. CONCLUSION: ER, PR, and HER2 by IHC in cell blocks of metastatic lymphnodes are reliable. Change in receptor (34.2%) and HER2 status (21.9%) was documented, which is of clinical significance as these patients warrant a change of management.

Pathology of Resin-Induced Gastrointestinal Damage: Report of 15 Cases and Review of Literature.

< strong > Objective: < /strong > Medication resins such as Kayexalate and Sevelamer used in the setting of chronic kidney disease for the correction of hyperkalemia and hyperphosphatemia are associated with gastrointestinal mucosal injury. In this study we describe the clinico-pathological features of Resin-induced gastrointestinal mucosal injury highlighting the histo-morphological appearances and differential diagnoses. The aim of this study is to increase the awareness of pathologists and clinicians alike to an under-reported etiology and pattern of intestinal mucosal injury related to medical resin therapy which may at times pose a clinical emergency. < strong > Material and Method: < /strong > The archives of the Department of Histopathology, Mubarak Al Kabir hospital were analyzed for cases of resin-induced gastrointestinal mucosal injury between 2013 and 2018. < strong > Results: < /strong > Of the 15 cases, Kayexalate crystals were identified in 7 cases, Sevelamer in 5 cases and both together were seen in 3 cases. Resin crystals were identified in the gastric antrum&duodenum (3 cases), colon (9 cases in the left colon, 2 cases in the right colon) and anal canal (1 case). The histological tissue reactions included mucosal necrosis (1 case), inflammatory polyps (2 cases), mucosal ulcerations with granulation tissue formation (10 cases), perforation (1 case) , and luminal crystals (1 case). < strong > Conclusion: < /strong > Accurate and timely recognition of the resin crystals in biopsy samples with clinical correlation is mandatory to avoid serious complications.

Cytological challenges in the diagnosis of intrathyroidal parathyroid carcinoma: A case report and review of literature.

Parathyroid carcinoma is an uncommon malignancy and the probability of an intrathyroidal location is low. Fine needle aspirations (FNA) of these presumably "thyroid nodules" can lead to misinterpretation because of the similarities in cytological features of parathyroid and thyroid lesions. Despite limitations, USG guided FNA cytology remains the first line of investigation. We report a case of intrathyroidal parathyroid carcinoma presenting with hypercalcemia and elevated serum parathormone. Cytological findings attributed it to a possible parathyroid lesion and histopathology revealed a parathyroid carcinoma. It is reported due to its rare occurrence on FNA along with brief literature review.

2,8-Dihydroxyadenine Nephropathy Identified as Cause of End-Stage Renal Disease After Renal Transplant.

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder of uric acid metabolism that leads to formation and excretion of 2,8-dihydroxyadenine into urine. The low solubility of 2,8-dihydroxyadenine results in precipitation and formation of urinary crystals and renal stones. Patients with this disorder usually have recurrent nephrolithiasis and can develop nephropathy secondary to crystal precipitation in the renal parenchyma. The disease is most often underdiagnosed and can recur in renal transplant, causing graft failure. Lack of specific clinical manifestations, chemical and radiologic features identical to those shown with uric acid stones, and lack of awareness among clinicians are among the causes for the underdiagnoses of this treatable disease. Allopurinol, a xanthine dehydrogenase inhibitor, is the mainstay of treatment, supported by high fluid intake and dietary modifications. The possibility of adenine phosphoribosyl transferase deficiency should be considered in all cases of urolithiasis in children, patients with recurrent urolithiasis, and patients with urolithiasis associated with renal failure of unknown cause, including patients with end-stage renal disease and renal transplant recipients. Here, we report a case of a 41-year-old female patient who had a late diagnosis of 2,8-dihydroxyadenine nephropathy-induced end-stage renal disease, made on the native nephrectomy that accompanied the renal transplant, and who had a timely intervention that prevented recurrence in the graft.

Insulin Prevents Hyperfiltration and Proteinuria but Not Glomerular Hypertrophy and Increases Mesangial Matrix Expansion in Diabetic Rats.

OBJECTIVE: The aim of this work was to study the effect of 7 days of strict glycemic control with insulin on glomerular function and structure in streptozotocin (STZ)-diabetic rats. MATERIALS AND METHODS: Three groups of adult male Fischer rats were studied: controls (n = 15), diabetics (n = 15), and insulin-treated diabetics (n = 15). Diabetes was induced by treating the rats with STZ (55 mg/kg i.p.). One week after the induction of diabetes, blood glucose, protein excretion rate (PER), glomerular filtration rate (GFR), and renal plasma flow (RPF) were estimated in each group. Furthermore, morphometric analysis was performed to estimate the tuft volume and changes in mesangial matrix area. The results are expressed as the mean ± SEM. RESULTS: STZ diabetes caused significant increases in GFR (0.89 ± 0.1 to 1.21 ± 0.1 mL/min/100 g; p < 0.01) and RPF (1.78 ± 0.37 to 3.32 ± 0.6 mL/min/100 g; p < 0.05). Furthermore, the diabetic rats had higher glomerular volumes but mesangial matrix areas similar to controls. Insulin treatment prevented the increases in blood glucose (4.5 ± 0.2 mM), PER (66.1 ± 7.8 mg/day), GFR (0.6 ± 0.07 mL/min/100 g), and RPF (1.72 ± 0.36 mL/min/100 g), but did not prevent glomerular hypertrophy (21.7% increase), but induced mesangial matrix expansion (25% increase). CONCLUSIONS: Insulin prevented the diabetes-induced hyperfiltration and proteinuria, but did not prevent glomerular growth, and induced mesangial expansion. Hyperglycemic episodes could be partly responsible for persistent glomerular growth and accelerated mesangial growth.

Metastatic breast carcinoma in pleural fluid: Correlation of receptor and HER2 status with the primary carcinoma-a pilot study.

BACKGROUND: Documenting the four molecular subtypes of breast carcinoma is significant as they determine response to therapy, disease free interval and survival. Our aim was to document the subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2): namely ER + PR+ HER2+; ER + PR + HER2-; ER-PR-HER2+; and ER-PR-HER2- in metastatic breast carcinoma in pleural fluid and compare them with their expression in the primary breast tumor. METHODS: Over a period of 18 months, 13 cases of invasive breast carcinoma with metastases to the pleural cavity were studied for subtypes. ER, PR, and HER2 were determined by IHC in the primary breast tumor and the cell blocks of the pleural fluid with metastatic carcinoma. RESULTS: Age ranged from 33 to 75 years. The primary tumor was ER + PR + HER2+; ER + PR + HER2-; ER-PR-HER2+ and ER-PR-HER2- in 2,9,0 and two cases, respectively while the metastatic tumor in pleural fluid was ER + PR + HER2+; ER + PR + HER2-; ER-PR- HER2+ and ER-PR-HER2- in 6, 3, 3, and 1, respectively. In five cases there was complete correlation between the primary and metastatic tumor. In 7 cases with HER2- primary tumor the metastases was HER2+. One from ER + PR+ HER2- primary tumor showed triple negative expression in the metastasis. CONCLUSIONS: Determining the molecular subtype in metastatic breast carcinoma is of importance as it affects the management. In our series 63% of metastatic tumors to the pleural fluid became HER2 positive and would thus require appropriate therapy. Diagn. Cytopathol. 2016;44:980-986. © 2016 Wiley Periodicals, Inc.

Gastrointestinal stromal tumour masquerading as a cyst in the lesser sac.

Gastrointestinal stromal tumours (GISTs) are solid tumours of the gastrointestinal tract, mostly found in the stomach and intestine. They rarely present as cystic lesions. A 74-year-old woman referred to the hepatopancreaticobiliary unit, with 3 months history of upper abdominal discomfort. Abdominal ultrasound scan showed a large cystic lesion in the epigastric region suggestive of a pancreatic pseudocyst. The CT-scan showed a 6.6×6×6.3 cm size cyst related to the pancreas and extending to the hepatogastric omentum. Endoscopic ultrasound (EUS) scan was suggestive of a pancreatic pseudocyst. Aspirated Cyst fluid via EUS showed benign cytology with normal amylase, lipase and tumour markers (CEA, CA-19.9 and CA-125). She was referred as a case of pancreatic pseudocyst. After surgical excision, the histopathology confirmed the presence GIST in the wall of the cystic lesion. The possibility of GIST should be kept in mind in the presence of unusual features of a cyst on abdominal imaging.

Epidermal growth factor receptor mutations in nonsmall cell lung carcinoma patients in Kuwait.

CONTEXT: Nonsmall cell lung carcinoma (NSCLC) is the most frequently diagnosed form of lung cancer in Kuwait. NSCLC samples from Kuwait have never been screened for epidermal growth factor receptor (EGFR) gene aberration, which is known to affect treatment options. AIMS: This study investigated the feasibility of using fine-needle aspiration (FNA) material for mutational screening, and whether common EGFR mutations are present in NSCLC samples from Kuwait. SETTINGS AND DESIGN: Eighteen NSCLC samples from five Kuwaitis and 13 non-Kuwaitis were included in this study. MATERIALS AND METHODS: DNA was extracted from FNA cell blocks and screened for EGFR gene mutations using peptide nucleic acid (PNA)-clamp assay, and EGFR gene amplification using fluorescent in situ hybridization (EGFR-FISH). EGFR protein expression was assessed using immunohistochemistry. RESULTS: Five EGFR mutations were detected in five non-Kuwaiti NSCLC patients (27.8%). EGFR gene amplification was evident in 10 samples (55.5%) by direct amplification or under the influence of chromosomal polysomy. Four samples had EGFR mutations and EGFR gene amplification, out of which only one sample had coexisting EGFR overexpression. CONCLUSIONS: Given the evidence of EGFR gene alterations occurring in NSCLC patients in Kuwait, there is a need to incorporate EGFR gene mutational screen for NSCLC patients to implement its consequent use in patient treatment.

Prevalence and correlation of human papilloma virus and its types with prognostic markers in patients with invasive ductal carcinoma of the breast in kuwait.

OBJECTIVES: This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. METHODS: The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. RESULTS: The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P <0.001). HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters. CONCLUSION: The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected.

Subclassification of pulmonary non-small cell lung carcinoma in fine needle aspirates using a limited immunohistochemistry panel.

BACKGROUND: Newer treatment modalities require subtyping of non-small cell lung carcinomas (NSCLC). Morphological differentiation is often difficult and various immunohistochemical (IHC) panels have been used to maximize the proportion of accurately subtyped NSCLC. AIM: The aim of this study was to subtype NSCLC on fine needle aspirates (FNA) using a minimal antibody panel. MATERIALS AND METHODS: Cell blocks from 23 FNA samples with a morphological diagnosis of NSCLC were taken. IHC was evaluated (blinded to clinical data) for thyroid transcription factor-1 (TTF-1), cytokeratin (CK)7, CK20, and tumor protein p63. RESULTS: TTF-1 was positive in 14 and negative in 9 cases. The p63 was positive in two cases each of TTF-1 positive and negative tumors. CK7 was positive in 12 of the 14 TTF-1 positive tumors and 4 of the TTF-1 negative tumors. CK20 was negative in all. All the 14 TTF-1 positive tumors were primary lung tumors, 12 being NSCLC and 2 being squamous cell carcinoma. Five of nine TTF-1 negative tumors were metastatic tumors from endometrium, kidney, and head and neck region (two), and one was an unknown primary. Four of the nine TTF-1 negative tumors were morphologically NSCLC and were clinically considered to be primary lung tumors. Three of these tumors stained positive for CK7 but negative for CK20 and p63, and one case was negative for the immunomarkers. CONCLUSION: Use of limited IHC panel helps categorize primary versus secondary tumors to the lung. The p63 is a useful marker for detecting squamous cell carcinoma. In countries where antibodies are not readily available, using a limited IHC panel of TTF-1, p63, and CK7 can help further type NSCLC lung tumors.

T-cell-rich B-cell lymphoma (TCRBCL): limitations in fine-needle aspiration cytodiagnosis.

Exclusive reports on fine needle aspiration (FNA) cytodiagnosis of T-cell-rich B-cell lymphoma (TCRBCL) are scarce in literature. This report reflects the diagnostic difficulties associated with cytodiagnosis of this rare variant of diffuse large B-cell lymphoma. The study is based on 11 cases with age ranging from 16 to 63 years and a median of 50 years. Male to female ratio was 6:5. Ten cases presented with lymphadenopathy and one had lymphadenopathy as well as extranodal solid tumor. The initial cytodiagnosis was suggestive of TCRBCL in one case, TCRBCL/Hodgkin's lymphoma (HL) in three cases, TCRBCL/HL/anaplastic large cell lymphoma (ALCL) in two cases, TCRBCL/ALCL in one case, and TCRBCL/non-Hodgkin lymphoma (NHL) T-cell/ALCL in one case. There was also a cytologically diagnosed HL case, which on review turned out to be HL/TCRBCL. Histopathological diagnosis was HL in all these nine cases. There were two histologically diagnosed TCRBCL cases during this period, with cytodiagnoses of NHL other than TCRBCL in one and HL in the other. While highlighting the difficulties associated with the cytodiagnosis of TCRBCL, this study conveys a word of caution that adequate immunocytochemical studies should be performed before diagnosing this rare neoplasm with a varied cytomorphology.

Impaired TGF-ß signaling and a defect in resolution of inflammation contribute to delayed wound healing in a female rat model of type 2 diabetes.

Wound healing (WH) impairment is a well-documented phenomenon in clinical and experimental diabetes. Sex hormones, in addition to a number of signaling pathways including transforming growth factor-ß1 (TGF-ß1)/Smads and TNF-α/NF-κB in macrophages and fibroblasts, appear to play a cardinal role in determining the rate and nature of WH. We hypothesized that a defect in resolution of inflammation and an enhancement in TNF-α/NF-κB activity induced by estrogen deficiency contribute to the impairment of TGF-ß signaling and delayed WH in diabetes models. Goto-Kakizaki (GK) rats and full thickness excisional wounds were used as models for type 2 diabetes (T2D) and WH, respectively. Parameters related to the various stages of WH were assessed using histomorphometry, western blotting, real-time PCR, immunofluorescence microscopy and ELISA-based assays. Retarded re-epithelialization, suppressed angiogenesis, delayed wound closure, reduced estrogen level and heightened states of oxidative stress were characteristic features of T2D wounds. These abnormalities were associated with a defect in resolution of inflammation, shifts in macrophage phenotypes, increased ß3-integrin expression, impaired wound TGF-ß1 signaling (↓p-Smad2/↑Smad7) and enhanced TNF-α/NFκB activity. Human/rat dermal fibroblasts of T2D, compared to corresponding control values, displayed resistance to TGF-ß-mediated responses including cell migration, myofibroblast formation and p-Smad2 generation. A pegylated form of soluble TNF receptor-1 (PEG-sTNF-RI) or estrogen replacement therapy significantly improved re-epithelialization and wound contraction, enhanced TGFß/Smad signaling, and polarized the differentiation of macrophages toward an M2 or "alternatively" activated phenotype, while limiting secondary inflammatory-mediated injury. Our data suggest that reduced estrogen levels and enhanced TNF-α/NF-κB activity delayed WH in T2D by attenuating TGFß/Smad signaling and impairing the resolution of inflammation; most of these defects were ameliorated with estrogen and/or PEG-sTNF-RI therapy.

Genotypic and phenotypic differences between nodal and extranodal diffuse large B-Cell lymphomas.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases that have diverse clinical, pathological, and biological features. Here, it is shown that primary nodal and extranodal DLBCLs differ genomically and phenotypically. Using conventional comparative genomic hybridization (CGH), the authors assessed the chromosomal aberrations in 18 nodal, 13 extranodal, and 5 mixed DLBCLs. The results demonstrate significantly distinct chromosomal aberrations exemplified by gains of chromosomal arms 1p, 7p, 12q24.21-12q24.31, and 22q and chromosome X and loss of chromosome 4, 6q, and 18q22.3-23 in extranodal compared with nodal DLBCLs. Nodal DLBCLs showed an increased tendency for 18q amplification and BCL2 protein overexpression compared with extranodal and mixed tumors. Using a panel of five antibodies against GCET1, MUM1, CD10, BCL6, and FOXP1 proteins to subclassify DLBCLs according to the recent Choi algorithm, the authors showed that the genomic profiles observed between the nodal and extranodal DLBCLs were not due to the different proportions of GCB vs ABC in the two groups. Further delineation of these genomic differences was illuminated by the use of high-resolution 21K BAC array CGH performed on 12 independent new cases of extranodal DLBCL. The authors demonstrated for the first time a novel genome and proteome-based signatures that may differentiate the two lymphoma types.

Reassessment of estrogen receptor expression in human breast cancer cell lines.

BACKGROUND: Human breast cancer cell (BCC) lines are used extensively in biomedical research and are classified as estrogen receptor (ER)-positive or ER-negative. We used flow cytometry (FCM), reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB) to assess ER expression in human BCC lines reported as being ER-positive (MCF7, T-47D, ZR-75-1) or ER-negative (MDA-MB-231, SK-BR-3, MDA-MB-453, HCC1954) to determine the validity of this classification. MATERIALS AND METHODS: ER was assessed in permeablized, fixed cells by FCM using two monoclonal anti-ERα antibodies and a polyclonal anti-ERß antibody, in parallel with RT-PCR and WB. RESULTS: All of the cell lines expressed ERα and ERß. Indirect immunofluorescence indicated that it was membrane and cytoplasmic ER that was being detected by FCM. Down-regulation by fulvestrant confirmed it was ER. CONCLUSION: These results demonstrate the importance of reassessing the ER status of human BCC lines that are used widely in biomedical research.

Analysis of estrogen receptor isoforms and variants in breast cancer cell lines.

In the present study, the expression of estrogen receptor (ER)α and ERß isoforms in ER-positive (MCF7, T-47D and ZR-75-1) and ER-negative (MDA-MB-231, SK-BR-3, MDA-MB-453 and HCC1954) breast cancer cell lines was investigated. ERα mRNA was expressed in ER-positive and some ER-negative cell lines. ERα Δ3, Δ5 and Δ7 spliced variants were present in MCF7 and T-47D cells; ERα Δ5 and Δ7 spliced variants were detected in ZR-75-1 cells. MDA-MB-231 and HCC1954 cells expressed ERα Δ5 and Δ7 spliced variants. The ERß1 variant was expressed in all of the cell lines and the ERß2 variant in all of the ER-positive and some ER-negative cell lines (MDA-MB-231, MDA-MB-453 and SK-BR-3). MCF7, ZR-75-1, MDA-MB-453, HCC1954 and T-47D cells expressed ERß5. All cell lines expressed an ERα 66-kDa protein band, and some expressed the truncated 42-kDa variant. ERß1 was detected in all of the cell lines in addition to a 38-44 kDa variant. The results indicate that breast cancer cell lines widely used in research and reported as being ER-negative express ERα and/or ERß mRNA and protein.

Real-time PCR: detection of oestrogen receptor-alpha and -beta isoforms and variants in breast cancer.

BACKGROUND: Splice variants exist for both alpha and beta oestrogen receptors (ERs). Oestrogen function results from a balance between the wild-type ERs (wt) and their variants. PATIENTS AND METHODS: Forty formalin-fixed paraffin-embedded breast cancer samples were analysed by real-time PCR using ERα primer sets detecting wt and exon-deleted 3, 5, 6 and 7 variants. The ERß primer sets detected wt ERß1 and ERß2 and ERß5 variants. At the end of the PCR cycles, a dissociation curve was generated showing the peaks for each sample at specific melting temperatures (Tm); finding more than one peak indicated the presence of variants. RESULTS: Many samples expressed both wt ER isoforms and their variants. The Tm value served as a cut-off point for determination of wt versus variant ER expression. CONCLUSION: This method of detection of wt and variant ER could help in patient selection for anti-oestrogen therapy and in monitoring response to therapy.

Papillary thyroid carcinoma: how much should the surgeon read from fine needle aspiration cytology reports?

OBJECTIVE: During routine fine needle aspiration cytodiagnosis of papillary thyroid carcinoma (PTC), a number of cases are diagnosed as suspicious; or it is suggested that PTC or a neoplasm be ruled out by histopathology. Since these diagnostic labels are likely to put the clinicians in a difficult situation while planning the management, this study aims to find out how much the surgeon should read from these reports. MATERIALS AND METHODS: The patients were divided into two groups. Group A included 38 cases diagnosed as PTC or suspicious of PTC. Group B included 40 cases in which it was suggested that PTC/a neoplasm to be ruled out and non-neoplastic lesions with one or more cytologic features of PTC. The two groups were compared with clinical, imaging and cytomorphologic features. RESULTS: A significant difference was observed with respect to age between Group A and Group B (P<0.001). The frequency of the following five cytologic features was significantly higher in Group A: papillary formation (P<0.001), psammoma bodies (P=0.054), fine nuclear chromatin (P=0.010), frequent nuclear grooves (P<0.001) and intra-nuclear cytoplasmic inclusion (P<0.001). Three or more of the five cytologic features were also reported in significantly higher number of Group A cases (P<0.001). Majority (81.8%) of the cases with subsequent histology in Group A were confirmed as PTC as opposed to 7.7% in Group B (P<0.001). CONCLUSIONS: Thus, cases with definitive cytodiagnosis of PTC and suggestive of PTC (Group A) should be taken much more seriously by the surgeons as compared to Group B cases.