Expression of androgen receptor and its regulatory molecule Lin28 in non-luminal subtype breast cancer.

Androgen receptor (AR) was associated with favourable outcome in luminal breast cancer. However, the role of AR in non-luminal breast cancer remains inconclusive. The aim of the present study was to evaluate the clinical significance of the AR and its regulatory pathway in non-luminal subtypes of breast cancer. In total, 284 breast cancer patients were recruited from January 2007 to January 2016. Tissue microarrays were constructed from archival paraffin blocks and assessed for AR and its regulatory molecule, Lin28, by immunohistochemistry. The association between AR and Lin28 expression and clinicopathological parameters was analyzed. Results showed that AR and Lin28 were co-expressed. No association between these proteins and clinicopathological parameters, and survival outcome was found. However, a higher proportion of the patients with AR and Lin28 expression were observed in HER2 subtype. In conclusion, Lin28 may be a novel marker for prognosis and targeted for treatment in HER2 subtype breast cancer.

Sectioning and extensively examining the fimbriated end (SEE-FIM) of the fallopian tube in routine practices, is it worth the effort?

AIM: To determine the prevalence of fallopian tube high-grade serous carcinoma (HGSC) and to analyze the benefit of the sectioning and extensively examining the fimbriated end (SEE-FIM) protocol. METHODS: Fallopian tubes from 450 patients with risk-reducing salpingo-oophorectomy, or tumor of the ovary, endometrium, fallopian tube or peritoneum were examined using the SEE-FIM protocol. Microscopic tubal pathology and the number of paraffin blocks used were evaluated. Immunostaining for p53 was performed to confirm TP53 mutation. Cost effectiveness was determined by equation of incremental cost-effectiveness ratio. RESULTS: Tubal HGSC were detected in 25 out of 70 cases of pelvic extrauterine HGSC, in 1 case of endometrioid carcinoma, and 4 cases of uterine serous carcinoma out of 250 cases of endometrial neoplasm. The mean number of tissue blocks per case was 6. The incremental cost for detecting one case of coexisting fallopian tube HGSC in the study population was 94 Thai baht/3 USD per case. CONCLUSION: The SEE-FIM protocol facilitates identification of lesions that are not distinguishable by classical sampling protocol, and this results in more accurate tumor staging and a better understanding of the carcinogenesis. The benefit of the SEE-FIM protocol was demonstrated, especially in cases at high risk for coexisting fallopian tube carcinoma.

Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients.

Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

Inferior Vena Cava Tumor Thrombosis Secondary to Metastatic Uterine Cancer: A Rare Cause of Sudden Unexpected Death.

Pulmonary tumor thromboembolus (PTTE) secondary to uterine cancer is a rare cause of sudden unexpected deaths in the elderly population. Additionally, tumor extension to the inferior vena cava (IVC) makes it rarer. No such cases have been previously reported in the forensic literature. We report this phenomenon in a previously healthy 70-year-old woman with no other known risk factors for the development of deep vein thrombosis. The deceased was found dead while watching television with her relatives. Autopsy examination revealed that her death was attributed to a saddle embolus lodged in the main pulmonary arteries. A uterine tumor was discovered, and microscopic examination revealed low-grade endometrial stromal sarcoma with angiolymphatic invasion. The tumor cells were also found in the embolus and the remnant thrombosis attached to the inner wall of the IVC. This case demonstrates a sudden unexpected death caused by acute PTTE following seeding of uterine cancer into the IVC and raises awareness of such events.

Inflammatory Breast Cancer from Metastatic Ovarian Cancer.

Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2-1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03-0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment.

High vascular endothelial growth factor gene expression predicts poor outcome in patients with non-luminal A breast cancer.

Breast cancer is the most frequent type of cancer among women worldwide. Vascular endothelial growth factor (VEGF), the key modulator of angiogenesis, has been implicated in breast cancer susceptibility and aggressiveness. VEGF expression was determined in 99 breast cancer tissue samples using reverse transcription-polymerase chain reaction and the human epidermal growth factor receptor 2 (HER2) status was determined by immunohistochemistry. Subsequently, the associations of VEGF, HER2 and hormone receptor status with clinicopathological data were evaluated. High VEGF expression was found to be significantly correlated with the presence of lymphovascular invasion. In hormone receptor-positive/HER2-positive, HER2-positive and triple-negative breast cancer, high VEGF expression was correlated with the presence of axillary nodal metastasis and lower overall survival rates. Therefore, the assessment of the VEGF status along with the hormone receptor and HER2 status may help identify high-risk patients who may benefit from anti-VEGF treatment.

Histologic evaluation of sentinel and non-sentinel axillary lymph nodes in breast cancer by multilevel sectioning and predictors of non-sentinel metastasis.

Sentinel lymph node (SLN) provides accurate nodal staging for breast cancer. This technique has been introduced in Siriraj Hospital since 1998. The goal of this study is to assess its accuracy in predicting the state of the axilla, and compare the results of standard examination and multilevel sectioning. A retrospective analysis of 195 breast cancer patients who underwent both SLN biopsy (using dye alone as the lymphatic mapping) and axillary node dissection during 1998-2002 were analyzed. All slides including SLNs and the non-SLNs (NSLNs) were reviewed and multilevel study was performed on all SLNs and NSLNs [four levels of hematoxylin-eosin (HE) at 200 µm interval and keratin stains on the first and fourth levels]. Of 195 patients, 30% of cases were SLN-positive (32 NSLN-positive and 27 NSLN-negative). Additional study could detect positive axillary nodes 10.8% (4 SLN-positive and 5 NSLN-positive) more than standard HE stain. The false negative rate increased from 20.3% to 24.1%. The concordance between SLN and NSLN statuses was 89.7%. The sensitivity was 75.9%. By multivariate analysis, the significant predictors for axillary node metastasis were tumor size of more than 2.2 cm, histologic type of invasive ductal carcinoma (IDC), not otherwise specified (NOS) and lymphovascular invasion (LVI). By univariable analysis, the significant predictors of NSLN metastasis after positive-SLN were outer location of the tumor, LVI and perinodal extension. In conclusion, use of multilevel and immunohistochemistry increased detection of positive-SLNs. Caution should be kept in accepting SLN biopsy using peritumoral dye technique alone as the procedure for staging due to a high false-negative rate. The concordance rate of 89.7% confirmed the reliability of SLN. Outer location of tumor, LVI and perinodal extension is significant predictors of positive-NSLN after positive-SLN.

Clinicopathologic features of breast carcinomas classified by biomarkers and correlation with microvessel density and VEGF expression: a study from Thailand.

BACKGROUND: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. MATERIALS AND METHODS: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER) +, HER2-, Ki-67≤14%], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. RESULTS: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. CONCLUSIONS: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

Vascular endothelial growth factor polymorphisms affect gene expression and tumor aggressiveness in patients with breast cancer.

Vascular endothelial growth factor (VEGF) is one of the key modulators of angiogenesis. The highly polymorphic promoter and 5' untranslated region of VEGF have been associated with susceptibility to and aggressiveness of several types of cancer. To examine the functional role of VEGF polymorphisms at -634 and -1498 positions, VEGF mRNA and protein in breast cancer tissues were analyzed by quantitative polymerase chain reaction and immunohistochemistry. A dual-luciferase assay was performed to determine promoter activity. The VEGF-634CC genotype demonstrated the highest VEGF mRNA expression. High VEGF mRNA expression was correlated with a tumor size of >2 cm, the presence of lymphovascular invasion and the presence of axillary nodal metastasis. The promoter containing the -1,498T/-634C haplotype exhibited the highest basal promoter activity. These findings suggest that the interaction between -1,498T and -634C polymorphisms increases VEGF expression and is involved in breast cancer aggressiveness.

Vascular endothelial growth factor ­634G/C polymorphism is associated with increased breast cancer risk and aggressiveness.

Polymorphisms in the promoter and 5' untranslated region of vascular endothelial growth factor (VEGF) have been associated with VEGF levels. To investigate the role of VEGF polymorphisms in breast cancer, the VEGF ­2578C/A, ­1498C/T, ­1154G/A and ­634G/C polymorphisms were genotyped in 483 breast cancer patients and 524 healthy controls. VEGF mRNA levels in breast cancer tissue were determined using semi­quantitative RT­PCR. The genotypes, ­634G/C and ­634C/C, were associated with an increased risk for breast cancer when compared with the ­634G/G genotype. The VEGF ­634G/C genotype was associated with tumor size >20 mm, perineural invasion and stage II­IV. Individuals with ­634C/C had lower disease­free survival. Patients with the VEGF ­634C/C genotype exhibited the highest VEGF mRNA levels. High VEGF mRNA expression correlated with tumor size >20 mm, presence of lymphovascular invasion and axillary nodal metastasis. These observations suggested that VEGF ­634G/C polymorphisms have a significant role in breast cancer susceptibility and aggressiveness.

Neuroendocrine carcinomas of the uterine cervix: A clinicopathological study.

BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare entity of uterine cervical carcinoma. Most of them have a more aggressive course and worse prognosis than a common type squamous cell carcinoma. Therefore, precise diagnosis is very crucial. OBJECTIVE: To study clinicopathological correlation and immunohistochemistry of uterine cervical NEC MATERIAL AND METHOD: All primary uterine cervical carcinomas from a 51-month period were histopathologically reviewed. Suspicious NECs were retrieved and immunohistochemically studiedfor chromogranin, synaptophysin, non-specific esterase (NSE) and CD56. Clinical information including treatments and mean disease free survival time were obtainedfrom chart review RESULTS: Fourteen (3.5%) cases of NEC were identified from 389primary uterine cervical carcinomas between October 1, 2002 and December 31, 2006 and classified into small cell neuroendocrine carcinoma (SNEC, 8 cases), large cell neuroendocrine carcinoma (LNEC, 3 cases), mixed SNEC and adenocarcinoma (2 cases), and mixed SNEC anid squamous cell carcinoma (1 case). All NEC presented with abnormal vaginal bleeding. The median age was 44 years (34-75 years). Exophytic mass was noted in 11 patients (78.6%). Five patients (36%) had distant metastases. All cases were immunoreactive for at least two neuroendocrine markers. Nine cases (64.3%) were positive for chromogranin, 11 (78.6%) for synaptophysin, 12 (85. 7%) for NSE, and 11 (78.6%) for CD56. CD56 was positive in eight of 11 SNEC cases. The mean disease free interval and overall survival time were 17.5 and 23.9 months, respectively CONCLUSION: Neuroendocrine carcinoma of the cervix is rare and has poor prognosis. In addition to histopathology, panel ofimmunohistochemistry is mandatory in the diagnosis of neuroendocrine carcinoma. Varying results of immunohistochemistry may be found.

Accuracy of preoperative curettage in determining tumor type and grade in endometrial cancer.

OBJECTIVE: To compare the accuracy of tumor grade and type in endometrial cancer between samples from preoperative curettage and postoperative hysterectomy specimens. MATERIAL AND METHOD: From January 2002 to June 2006, 98 women diagnosed with endometrial cancer and treated in the Department of Obstetrics and Gynecology, Siriraj Hospital were included The comparisons of tumor types and grades were performed on both preoperative endometrial curettage and hysterectomy specimens; the relationships between the concordance rate and accuracy of types and grades were analyzed. RESULTS: Endometrial samples and the subsequent hysterectomy specimens from 98 patients were studied After exclusion of benign endometrial tissue sampling and no residual tumor in hysterectomy specimen and preoperative diagnosis from endometrial biopsy, 86 patients were analyzed The overall tumor type accuracy was 93.0% for endometrioid type. The comparative FIGO grades were analyzed between preoperative endometrial samplings and hysterectomy specimens. Accuracy was 74.0% for grade 1, 75.3% for grade 2 and 90.4% for grade 3. The accuracy for grade 3 tumors was significantly higher than for grade 1. CONCLUSION: The authors should be careful in planning patient management based on the initial histological findings. It is important for clinicians to be aware that endometrial adenocarcinoma may show focal variation in tumor grade and to be aware of the limitation of examination of small tissue samples.

Reverse twin-twin transfusion syndrome after fetoscopic laser photocoagulation of chorionic anastomoses: a case report.

A case of severe twin-twin transfusion syndrome (TTTS) which developed at menstrual age of 17 weeks underwent a fetoscopic laser ablation of the anastomosing vessels. The vascular equator of the anastomoses was noticed to be deviated due to marginal cord insertion of the recipient fetus. The procedure was accomplished uneventfully. However, the recipient fetus died 6 h after the procedure. After the pregnancy was terminated, the donor was found to be counterintuitively plethoric, and the recipient was pale. Similar appearances were noted on the placental territories of each fetus. This is consistent with reverse TTTS. Dye injection study and microscopic examination revealed a residual deep vein-vein anastomosis. This subchorionic vascular connection is still a challenge to coagulate with current placental surgery techniques. To the best of our knowledge, this is the first confirmed case of reverse TTTS as a cause of fetal loss following laser photocoagulation. This report also discusses the technical considerations in the complicated case of in utero placental surgery for TTTS.

Cushing's syndrome caused by an ACTH-producing ovarian steroid cell tumor, NOS, in a prepubertal girl.

Ectopic ACTH syndrome is a very rare cause of pediatric Cushing's syndrome. And if present, bronchial or thymic carcinoids predominate as causes. We hereby demonstrate a first case report of ACTH-producing ovarian steroid cell tumor, NOS, causing ectopic ACTH syndrome in a prepubertal girl.

Interobserver reproducibility in determining p16 overexpression in cervical lesions : use of a combined scoring method.

OBJECTIVES: To evaluate interobserver reproducibility of a combined scoring method for immunohistochemical interpretation of p16 overexpression in cervical lesions. MATERIALS AND METHODS: p16 immunostaining was performed in cervical samples from 183 patients, including 69 normal, 42 low grade squamous intraepithelial lesions(LSIL), 36 high grade SIL (HSIL), and 36 squamous cell carcinomas(SCCAs). Each case was evaluated by a combined scoring method based on the percentage of positive cells (score 0-3), the intensity of staining (score 0-3), and the distribution pattern (score 0-2). Immunoexpression for p16 was considered as positive when the combined score was 4-8 and negative with a score of 0-3. Ten pathologists with varied experience in interpretating p16 immunostains evaluated each slide independently. RESULTS: All normal cervical squamous epithelia (69/69) were uniformly negative for p16. All HSILs (36/36), all SCCAs (100/100), and all but one of the LSILs (40/41, 97.6%) showed positive expression. In 172 of 183 cases (93.9%), p16 interpretation was concordant with all pathologists. Eleven cases with discordant results included 10 LSILs and 1 normal mucosa sample. Percentage of agreement of each pathologist pair ranged from 96.7-100% (mean 98.1%) with mean kappa value of 0.96 (range 0.93-1.000). CONCLUSION: The proposed combined scoring method shows good reproducibility among the participating pathologists and good correlation with the histologic diagnosis. This method may be a useful guide in the interpretation of p16 expression in cervical epithelial lesions.

Surgical pathology and etiology of 278 surgically removed mitral valves with pure regurgitation in Thailand.

INTRODUCTION: There are multiple causes of mitral regurgitation. Its etiology includes floppy valve, postinflammatory disease, infective endocarditis, and other disorders. Recently, there has been an increased tendency to remove only portions of the mitral valve, causing difficulty in the determination of etiology. Our objective was to study the pathology and etiology of mitral regurgitation from surgically removed specimens. METHODS: Native mitral valve specimens surgically excised due to mitral insufficiency were examined. Etiology was determined according to macroscopic, microscopic, clinical, and operative findings. RESULTS: Among 278 mitral valve specimens, 43% were classified as floppy valve, 31% as postinflammatory disease (presumably associated with rheumatic fever), 12% as infective endocarditis, and 14% as miscellaneous group. In floppy valves, diffuse myxoid change and chordal rupture were the main findings. In postinflammatory disease, moderate neovascularization and chronic inflammatory cell infiltration were most commonly found. Aschoff bodies were found in two cases. In infective endocarditis, gram-positive cocci were found in 70% of cases. In the miscellaneous group, three cases were related to Marfan syndrome and one case was related to papillary muscle necrosis. In comparison with postinflammatory disease, the posterior leaflet in the floppy valve had a significantly longer basal free-edge length, a more frequent chordal rupture, and an higher mean age of patients. Among completely and partially excised specimens with postinflammatory disease, there were no significant differences in microscopic findings. CONCLUSION: The three most common etiologies in mitral regurgitation were floppy valve, postinflammatory disease, and infective endocarditis. Macroscopic, microscopic, clinical, and operative findings are important in the evaluation of etiology, especially in partially excised specimens.

Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome presenting with a large nephrogenic cyst, severe oligohydramnios and hydrops fetalis: a case report and review of the literature.

OBJECTIVES: To report a case of EEC syndrome with a large nephrogenic cyst detected by prenatal ultrasonography. METHODS: Prenatal ultrasonographic detection, genetic counselling, termination of pregnancy, radiographic study, autopsy and ultrastructural study of scalp hair. The literature on EEC syndrome with genitourinary anomalies and prenatal diagnosis was also reviewed. RESULTS: A 6-cm cyst in the right side of abdominal cavity was detected in a fetus of 24 weeks' gestational age with severe oligohydramnios and hydrops fetalis. The autopsy revealed bilateral renal dysplasia with a large nephrogenic cyst at the right side and markedly hypoplastic urinary bladder and pulmonary hypoplasia. The fetus also had ectrodactyly and syndactyly of hands and feet and ectodermal dysplasia and left cleft lip and palate. Ultrastructure of hair from scanning electron microscopy revealed no obvious abnormality. CONCLUSION: This is a rare case of fetal malformation partly detected prenatally. In order to detect this syndrome, careful ultrasound search for acral anomalies should be performed in cases with renal malformation or obstructive uropathy.

Angiogenesis in stage IIIB squamous cell carcinoma of uterine cervix: reproducibility of measurement and preliminary outcome as a prognostic factor.

This study was performed to determine the reliability and replicability of IMD analysis using the Factor VIII immunohistochemical method. The following purpose was determining the relationship between IMD and clinical outcome in individual cervical cancer patient treated with radical radiotherapy. Twenty nine patients with stage IIIB cervical cancer were enrolled. Phase one was performed by using two pieces of tissue biopsy from different locations in the tumor from each patient. The IMD value was counted by the two pathologists after counterstaining by Factor VIII immunohistochemical method. No interobserver disagreement between the two pathologists was found (correlation coefficient = 0.92, 95% CI 0.82-0.96 for the first piece of tissue and 0.85, 95% CI 0.67-0.93 for the second piece). There was no variability in the IMD between the 2 pieces of tissue specimens from different locations of the tumor Phase two followed to evaluate the relationship between IMD and clinical outcome in individual cervical cancer patients. Because of the small sample size, different patients' characteristics, different treatment protocol and short term follow up, there is no statistically significant conclusion.

Pathology and etiology of 110 consecutively removed aortic valves.

OBJECTIVES: To study the pathology and determine the etiology and prevalence of aortic valve disease from surgically removed aortic valve specimens. MATERIAL AND METHOD: All the native surgically excised aortic valves (AV) received from June 1997 to March 1999 (22 months) were studied macroscopically including cuspal measurements and microscopically. By preoperative echocardiographic and macroscopic studies, they were classified into functional disorders of predominant aortic stenosis (AS), aortic stenosis with regurgitation (AS-AR) and predominant aortic regurgitation (AR). The patients' medical records were reviewed and the clinical information was extracted. The etiology was determined according to the macroscopic, microscopic and clinical findings. RESULTS: Among 110 AV (76 isolated AV and 34 with concomitant mitral valves from patients aged 15-96 years, mean age 47.54 years; male:female = 1.39:1) there were 25 AS (22.73%), 34 AS-AR (30.91%) and 51 AR (46.36%) cases. Eighty-four (76.36%) were tricuspid, 16 (14.54%) were bicuspid and 10 were undetermined. Cuspal measurements of each disease were provided and compared. All AS specimens were related to moderate to severe calcification and causes included postinflammatory disease (14 cases, 56%; age range 38-67 years, mean age 53.29 years, male:female = 0.56:1), degenerative calcific change (11 cases, 44%, age range 56-76 years, male:female = 1.2:1; mean age 69 years of 5 tricuspid AV and 60.83 years of 6 bicuspid AV). In AS-AR, 29 cases (85.29%; mean age 47.10 years; male:female = 1.23:1) were attributable to postinflammatory disease and 5 cases (mean age 70.20 years; male:female = 1.5:1) to degenerative calcific change. In pure AR, there were 21 cases (age range 15-65 years, mean age 29.76 years) of postinflammatory disease, 14 cases of infective endocarditis (IE) and postIE (age range 20-63 years, mean age 42.21 years; all 10 IE cases contained gram positive cocci), 1 case (age 55 years) of bicuspid calcific change, 8 cases of AV with dilated valve ring, 5 cases of miscellaneous causes and 2 cases of indeterminate etiology. Aschoff bodies were found in 3 AR cases. Four of 18 postinflammatory AS-AR and 4 of 14 postinflammatory disease AR cases had past history of rheumatic fever. One postinflammatory AS also had infective endocarditis from gram positive cocci without clinical sign. Severe degenerative calcific change had a higher incidence of underlying diabetes (3 of 15 cases, 20%), hypertension (8 of 14 cases, 57.14%) and dyslipoproteinemia (9 of 13 cases, 69.23%) in comparison with 3.37% (3/89) for diabetes, 9.09% (8/88) for hypertension and 30.99% (22/71) for dyslipoproteinemia in other AV diseases in combination. CONCLUSION: The three common causes of severe AV functional disorders were postinflammatory disease (58.18%), degenerative calcific change (15.45%) and IE-postIE (12.72%). Underlying diseases of severe degenerative calcific change included hypertension, dyslipoproteinemia and diabetes. Macroscopic and microscopic examinations together with clinical information, echocardiographic findings and operative details are important in evaluating the etiology of valvular diseases especially in severely calcified specimens.