Overexpression of c-Myc in primary central nervous system lymphoma of Thais.

BACKGROUND: c-Myc protooncogenes have been implicated in the tumourigenesis of extracerebral lymphomas, however only afew studies on this oncogenic molecule have been available for primary central nervous system lymphoma (PCNSL). OBJECTIVE: To determine the prevalence ofprotein overexpression and gene amplification of c-Myc in PCNSL and to correlate with histological and immunophenotypic subtypes of malignant lymphoma according to WHO classification of tumors of haematopoietic and lymphoid tissue 2001. SETTING: King Chulalongkorn Memorial Hospital, Thailand. DESIGN: Descriptive study. MATERIAL: 25 Thai patients presented between 2001 and 2005. METHOD: The overexpression and amplification of c-Myc in malignant lymphoma were studied by means of immunohistochemistry and chromogenic in situ hybridization (CISH), respectively, in formalin-fixed, paraffin-embedded specimens. The histomorphology and immunohistochemistry were used to subclassify PCNSLs according to WHO classification 2001. RESULTS: Fourteen males and eleven females were recruited. They were between the ages of 21 and 86 years with the mean of 53 years. Eight had documented human immune deficiency virus (HIV) infection. Four of 17 immunocompetent cases overexpressed c-Myc protein without c-Myc gene amplification. No immunocompromised cases showed overexpression of c-Myc protein. All PCNSLs were classified as diffuse large B-cell lymphoma. CONCLUSION: In PCNSL, c-Myc overexpression is notfound immunocompromised (HIV-infected) patients and is found in 23.5% of the immunocompetent individuals without c-Myc gene amplification. All PCNSLs are diffuse large B-cell lymphoma according to WHO classification 2001.

RET proto-oncogene expression of papillary thyroid carcinomas in Thai patients.

BACKGROUND: Ret proto-oncogene activation has been found in papillary thyroid carcinoma with different frequencies according to geographic location. The rate of expression ranges from 0-100 percent in the literature. This gene expression has also been studied in many Asian countries but it has never been studied in Thailand. OBJECTIVE: To study the frequency of the RET expression and their roles in predicting prognosis of papillary thyroid carcinoma among Thai patients treated at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: One hundred and one cases of papillary carcinomas were studied with immunohistochemistry for RET antibodies. All slides with routine staining were reviewed to classify cell variants and record other prognostic parameters such as size, multicentricity, extrathyroid invasion. The clinical data such as age and sex were also included for analyses. RESULTS: Forty-seven of the total 101 cases (46.5%) showed positive RET protein staining. The mean age among patients with RET negative neoplasms was 43.9 years compared with 39.8 years in RET positive group (p = 0.16). The average size of the tumors without RET expression was 2.5 cm, slightly larger than the RET positive tumors (2.1 cm)(p = 0.26). Extrathyroid invasion of the RET-positive tumors was found to be 33.2 percent while the RET negative neoplasms had 38.8 percent of this feature (p = 1). According to AMES score, the RET positive cases had only 11 percent of high-risk tumors, whereas the RET negative group comprised 23.1 percent of high-risk malignancies (p = 0.20). There was no significant difference in RET expression among cell variants (p = 1). CONCLUSION: The study of 101 papillary thyroid carcinomas at the King Chulalongkorn Memorial Hospital disclosed high frequency of RET expression (46.5%) and this is the only data among Thai patients that has ever been documented in the literature. Although, the gene expression in the tumor tends to be associated with good prognostic features but it was not distinct enough to be statistically significant.

Citrate attenuates tubulointerstitial fibrosis in 5/6 nephrectomized rats by decreasing transforming growth factor-beta1.

OBJECTIVE: Tubulointerstitial fibrosis plays an essential role in progression to end stage renal disease (ESRD) in various chronic renal failure (CRF) models including the 5/6 nephrectomy (5/6). The present study examines the renoprotective effect of citrate in the renal ablative model that is quite similar to CRF in human. MATERIAL AND METHOD: Male Wistar rats underwent 5/6 and were fed with tap water (5/6tap) or tap water containing 67 mEq/L citrate solution (5/6cit). Sham-operated rats (S) were divided into Stap and Scit groups. Renal function, renal histopathology, renal alpha-Smooth muscle actin (SMA), and renal transforming growth factor (TGF)-beta1 were determined immediately and at the 8th week after operation. RESULTS: Following the surgery, the values of glomerular filtration rate (GFR) in the 5/6tap and the 5/6cit groups were 2.39 +/- 0.25 and 2.35 +/- 0.25 (mL/kg/min), respectively, both were significantly lower than sham groups (p < 0.05). At the eighth week, the 5/6tap group had progressively decreased GFR and had higher fibrosis score, increased alpha-SMA positive cells, and renal tissue TGF- beta1 when compared with the sham groups. The 5/ 6cit group, when compared with the 5/6tap group, had higher GFR (2.51 +/- 0.22 vs 1.17 +/- 0.33 mL/kg/min; p < 0.05), lower fibrosis score (1.83 +/- 0.88 vs 3.0 +/- 0.4, p < 0.001), lower alpha-SMA activity (159 +/- 2.9 vs 187 +/- 12.3 cells per 1000 interstitial cells, p < 0.05), and lower renal TGF-beta1 levels (1771.3 +/- 239.5 vs 4716.9 +/- 871.2 pg/mg protein, p < 0.005). CONCLUSION: As such, in 5/6 nephrectomized rats, citrate therapy for eight weeks could decrease tubulointerstitial fibrosis mainly by reducing the heightened renal TGF-beta1 levels and additionally by attenuating the increased myofibroblast activity.

Necrotizing non-granulomatous lymphadenitis: a clinicopathologic study of 40 Thai patients.

The purpose of this study was to describe the clinicopathological features of 40 cases of necrotizing non-granulomatous lymphadenitis in Thai patients. The clinical features, histomorphology and special stains were evaluated in 40 Thai patients from the pathology records of King Chulalongkorn Memorial Hospital from January 2001 to December 2003 in those diagnosed as having necrotizing non-granulomatous lymphadenitis. Of the 40 patients, 17 cases (42.5%) had Kikuchi-Fujimoto disease (KFD), 8 cases (20%) had tuberculosis (TB) lymphadenitis and 1 case (2.5%) had systemic lupus erythematosus (SLE) with associated lymphadenitis. Fourteen cases (35%) did not have a specific diagnosis due to a lack of follow-up data. KFD most commonly occurs in young women, and is characterized by the presence of coagulative necrosis and karyorrhexis often centered in the paracortex, an absence of neutrophils and plasma cells, proliferation of various cells composed of lymphocytes, histiocytes, immunoblasts and plasmacytoid monocytes and the absence of a granuloma. Tuberculous lymphadenitis usually occurs in women with a mean age of 34.25 years. The lymph nodes reveal extensive coagulative necrosis involving the cortex, paracortex and medulla, proliferation of mixed inflammatory cells, including neutrophils, lymphocytes and plasma cells in the necrotic area and the presence of proliferating histiocytes at the periphery of the necrotic area. The lymph nodes of SLE-associated lymphadenitis reveal large numbers of plasma cells and hematoxylin bodies. We suggest that necrotizing non-granulomatous lymphadenitis is not specific for any disease, but rather a common histologic change found in diseases, such as TB, SLE, and KFD. Further investigation to obtain a definite diagnosis should be done for appropriate treatment.

A two-phase study model for the standardization of HER2 immunohistochemical assay on invasive ductal carcinoma of the breast.

OBJECTIVES: To develop and verify a standardized protocol for HER2 immunohistochemical assays on invasive ductal carcinoma of the breast in Thailand. MATERIAL AND METHOD: A two-phase study approach was employed. In the Phase One, after verifying the proposed protocol that adopted the HercepTest procedure using readily available primary antibodies, CB11 and A0485, Lab 1 performed the HER2 immunohistochemical staining for 137 cases of invasive ductal carcinoma twice with two types of the antibody. Nine pathologists from 8 centers independently examined and scored all the 2 x 137 stained slides that were blinded for antibody type. Interobserver reliability was calculated using pair-wise kappa. Following discussion of the results, the Phase Two study was planned. Lab 2 and Lab 3 independently performed the HER2 staining according to the protocol for 60 invasive breast carcinoma cases. The same group of pathologists scored 2 x 60 stained slides that were masked for laboratories. Interobserver reliability and interlaboratory agreement from each pathologist were calculated using kappa statistics. Three interpreted categories--namely negative, equivocal and positive tests were used in the analyses. RESULTS: Phase One study showed interobserver agreement between pairs varied from kappa 0.75 (95%CI, 0.68-0.82) to 0.06 (95%CI, 0-0.14) while Phase Two study obtained pair-wise kappa scores ranged from 0.84 (95%CI, 0. 80-0.89) to 0. 65 (95%CI, 0.59-0.71). Interlaboratory kappa for each pathologist was 0.67 (95%CI, 0.61-0.73). CONCLUSION: The standardization of HER2 immunohistochemical assay was achieved through this two-phase study model. It had added benefits of improving pathologists' expertise and verifying the HER2 testing protocol to be used in Thailand.

Extranodal malignant lymphoma of the upper aerodigestive tract: prevalence of Epstien-Barr virus (EBV) infection in King Chulalongkorn Memorial Hospital.

BACKGROUND: High frequency of Epstein-Barr virus (EBV) in the normal mucosa of the upper aerodigestive tract suggests that it may serve as a reservoir for the virus. Malignant lymphomas arising in this site may be associated with EBV. OBJECTIVES: To determine the prevalence of EBV infection in extranodal malignant lymphomas of the upper aerodigestive tract. SETTING: King Chulalongkorn Memorial Hospital, Thailand. DESIGN: Descriptive study. PATIENTS: 42 Thai patients who presented between 1998 and 2003. MATERIAL AND METHOD: The expression of EBV mRNAs (EBERs) of malignant lymphoma was studied by means of in situ hybridization in formalin-fixed, paraffin-embedded specimens. RESULTS: The recruited subjects were 26 males and 16 females, and their age ranged from 3 to 85 years with the mean of 51.43 years, in 4 of them human immune deficiency virus (HIV) infection was documented. Ten of 42 cases (23.81%) expressed EBER transcripts and were extranodal NK/T-cell lymphomas, nasal type (7 cases), plasmablastic lymphomas (2 cases) and diffuse large B-cell lymphoma (1 case). Three of 4 cases (75%) of known HIV-seropositive cases were EBV-positive (2 plasmablastic lymphomas and 1 diffuse large B-cell lymphoma). CONCLUSION: In the upper aerodigestive tract, EBV was present in some but not all malignant lymphoma. It was associated with extranodal NK/T-cell lymphoma, nasal type and B-cell lymphoma arising in HIV-infected patients, but it was not found in B-cell lymphoma arising in immunocompetent patients.

Weekly rescreening of 10% of the total cervical Papanicolaou smears: a worthwhile quality assurance scheme.

BACKGROUND: In awareness of possible false negative cervical Papanicolaou tests in routine service, the authors developed and tested a new scheme that would be a practical adjunct in quality assurance. OBJECTIVE: To evaluate the value of a weekly rescreen of 10% of the total cervical Papanicolaou smears as a quality assurance scheme. DESIGN: A prospective descriptive study. RESULTS: Of 31,914 slides in the 9-month study period, a total of 3,097 slides (9.7%) were picked up in the rescreen scheme. There were 29 discordant cases (0.9%) consisting of 7 cases (0.2%) of errors from the initial reporting, 2 cases of errors from the rescreening and 20 other cases from disagreements on designating atypical squamous cells of undetermined significance. The errors of the initial reports could be further classified into 6 cases due to screening errors and one case because of interpretation error. The proper diagnoses had been revised and resent to the attending gynecologists. CONCLUSION: A weekly rescreening 10% of total cervical Papanicolaou smears scheme was worthwhile for quality assurance. It could be used for evaluating screener performance and create internal quality improvement. The detected false diagnoses were manageable.

Extranodal malignant lymphoma of the upperaerodigestive tract in King Chulalongkorn Memorial Hospital according to WHO classification.

BACKGROUND: The Working Formulation commonly used to classify NHL in Thailand has been recognized as imperfect for primary extranodal lymphoma, especially in head and neck regions. OBJECTIVE: To study the clinicopathological and immunohistochemical features of extranodal malignant lymphoma of the upper aerodigestive tract according to WHO classification. SETTING: King Chulalongkorn Memorial Hospital. DESIGN: Descriptive study. PATIENTS: 77 Thai patients who presented between 1998 and 2003. METHODS: Routine histology was performed and stained with H&E and immunohistochemistry, and clinical characteristics were recorded. RESULTS: The patients included 42 males and 35 females, with an average age of 53.87 years. Tumor sites were as follows: Waldeyer ring (n = 42, 54.55%), sinonasal areas (n = 19, 24.67%), oral cavity (n = 9, 11.69%), hypopharynx (n = 4, 5.19%), and larynx (n = 3, 3.90%). Immunohistochemically, 57 tumors (74.02%) were of B-cell phenotype and 19 tumors (24.68%) were of T-cell phenotype. According to the WHO classification, 45 cases (58.43%) were large B-cell, 3 (3.90%) were Burkitt, 3 (3.90%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), 4 (5.19%) were follicular lymphoma, 1 (1.30%) was precursor B-lymphoblastic lymphoma, and 1 (1.30%) were mantle cell lymphoma. Among the T-cell lymphomas, 9 (11.69%) were of peripheral T-cell lymphoma, unspecified, 9 (11.69%) were extranodal NK/T cell lymphoma, nasal type, and 1 (1.30%) were anaplastic large-cell lymphomas. In nasal cavity, 8 tumors (42.11%) were extranodal NK/T-cell lymphoma, nasal type, 5 (26.32%) were diffuse large B-cell lymphoma, 4 (21.05%) were peripheral T-cell lymphoma, unclassified, and 1 (5.26%) was Burkitt lymphoma. CONCLUSION: Our data correspond with series from Japan, Hong Kong, and Korea, but there is a significant difference from Western population in T-cell lymphomas of sinonasal area especially extranodal NK/T cell lymphoma of nasal type and peripheral T-cell lymphoma, unspecified which had a higher frequency in Thailand, Japan, Hong Kong, and Korea.

Mantle cell lymphoma in Thai patients.

Mantle cell lymphoma (MCL) is a disease entity recently introduced into the new lymphoma classification, therefore, the clinical features as well as therapeutic outcomes in Thai patients with MCL has never been described The authors herein retrospectively analysed 21 newly diagnosed patients with MCL at King Chulalongkorn Memorial Hospital from January 1997 to December 2002. The median age of the patients was 54 years (range, 38-79). Male:female was 4:1. Generalized lymphadenopathy (67%) was the most common presenting feature. The majority of patients (85%) had advanced disease (stage III, IV, Ann Arbor system). Fifty-six percent of the patients were classified as the high- and high-intermediate risk group by the international prognostic index. Most patients were treated with CHOP (vincristine, cyclophosphamide, doxorubicin, prednisolone) or CVP (vincristine, cyclophosphamide, prednisolone) regimen. The overall complete remission rate was 59%. With a median follow-up of 13 months (range, 1-62 months), the rates of overall, progression-free and disease-free survivals were 32%, 9% and 20%, respectively. Sixty-seven percent of the patients had relapse/progressive disease after follow-up. In conclusion, the clinical features as well as the outcomes of Thai patients with MCL were comparable to patients in Western countries. Newly diagnosed patients should be treated with novel modalities other than conventional CHOP chemotherapy in order to improve the outcomes.

Estrogen and progesterone receptors status in Thai female breast cancer patients: an analysis of 399 cases at King Chulalongkorn Memorial Hospital.

A retrospective review was performed on 576 patients who have been diagnosed breast cancer and referred to Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between January 1995-September 2001. There were three hundred ninety nine cases of invasive breast cancer that available for estrogen (ER) and/or progesterone (PR) receptor status. The mean and median age in our study were 49.6 year and 49.0 year respectively. About 60.9 per cent of the patients were pre and peri-menopause and 37.8 per cent were post-menopause. Most of the histological cell type were invasive ductal carcinoma which comprised of 92.7 per cent. Histologic grading were nearly equal for moderately and poorly differentiated grade: 43.66 per cent and 40.66 per cent. The results of our study showed 53.4 per cent of 399 patients had ER positive and 42.1 per cent of 380 patients had PR positive. The proportion of ER+PR+, ER+PR-, ER-PR+, and ER-PR- were 36.31 per cent, 15.53 per cent, 5.79 per cent and 42.37 per cent respectively. Older age and post-menopause women had higher ER+. While patients with increase tumor size, poorly differentiated grading, increase positivity of axillary lymph nodes and higher stage have more chance of ER negative and PR negative.