BACKGROUND: The catalytic subunit of telomerase, hTERT (telomerase reverse transcriptase), is one of the most important components of telomerase, and performs a pivotal role in the mechanism underlying the regulation of telomerase activity in cellular immortalization and carcinogenesis. The principal objective of this study was to investigate hTERT expression in patients with non-small cell lung carcinomas (NSCLCs), and to evaluate its clinical significance and association with the expression of p16 and p53. METHODS: Using tissue microarray, the protein expression profiles of hTERT, p16 and p53 were investigated via immunohistochemistry in 167 samples of NSCLCs. RESULTS: Expression was observed in 54.5% (91/167) of the tumors, which were predominantly squamous cell carcinomas. Patients evidencing hTERT expression in their tumors exhibited significantly poorer survival rates than did patients without hTERT expression in early-stage NSCLCs (p=0.0125). According to the results of our Cox regression analysis, hTERT expression proved to be an independent prognostic factor (p=0.006), particularly for squamous cell carcinomas (p=0.019). hTERT expression was not correlated with p16 expression, but was rather associated with the expression of p53 (p=0.002). CONCLUSIONS: Our results show that hTERT may perform a function in the progression of NSCLC, and that its detection may be useful in predicting the prognosis of NSCLC patients in the early stages of the disease, as well as in the development of a targeted therapy in these tumors.
Carcinogenesis ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Catalytic Domain ; Humans ; Immunohistochemistry ; Lung* ; Prognosis ; Survival Rate ; Telomerase*

Fibrous dysplasia is a common benign disorder of bone in which normal bone marrow is replaced with fibro-osseous tissue. As PET/CT is increasingly used for the staging of different malignant disease, incidentally found fibrous dysplasia with increased FDG uptake may mimic metastasis. We report on a 46-year-old woman with fibrous dysplasia who underwent PET/CT because of suspected recurrence of breast cancer and was misdiagnosed as a bony metastasis with a focal FDG uptake on left proximal femur. This lesion was interpreted as fibrous dysplasia based on MRI in addition to the plain radiographs. We conclude that MRI in addition to radiography may help to differentiate fibrous dysplasia mimicking metastasis on PET/CT in the patients with malignancy.
Bone Marrow ; Breast ; Breast Neoplasms ; Female ; Femur ; Humans ; Hydrazines ; Middle Aged ; Neoplasm Metastasis ; Recurrence

PURPOSE: Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain. RESULTS: Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post-NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002). CONCLUSION: In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.
Breast Neoplasms ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Lymphocytes, Tumor-Infiltrating ; Prognosis ; Triple Negative Breast Neoplasms

PURPOSE: This study was undertaken to observe the pattern of methylation of the p16INK4a and human telomerase reverse transcriptase (hTERT) genes and the p16 and hTERT protein expressions in invasive ductal carcinoma of the breast. In addition, we evaluated the relationship between the methylation status of the two genes and their protein expressions. METHODS: We performed methylation-specific PCR (MSP) and immunohistochemical staining in 63 breast cancer specimens. RESULTS: There was no statistical association between p16INK4a gene methylation and the histological grade (tumor grade, tumor size and lymph node status). Methylation of the hTERT promoter did show significant differences according to the histological tumor grade and tumor size, but there was no clinical significance. Methylation of the p16INK4a and hTERT genes was found in 22.2% and 31.8% of the specimens, respectively. A negative p16 protein expression (0-10% expression rate) was observed in 38.1% of the specimens (24 of 63). A positive hTERT expression (more than a 25% expression rate) was observed in 73.0% of the specimens (46 of 63). There was no statistical significance in the relationship between the methylation status and the protein expression. CONCLUSION: Our data suggest that methylation of the p16 and hTERT genes is not associated with their protein expressions according to Immunohistochemisty. There seemed to be another complicated mechanism for p16 inactivation and hTERT activation in breast cancer.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Genes, p16 ; Humans* ; Lymph Nodes ; Methylation ; Polymerase Chain Reaction ; Telomerase

The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Transitional Cell/*metabolism/mortality/pathology ; Cyclin D1/*metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Recurrence ; Retinoblastoma Protein/*metabolism ; Survival Rate ; Tumor Suppressor Protein p53/*metabolism ; Urinary Bladder Neoplasms/*metabolism/mortality/pathology

We report a case of Warthin's tumor of the parotid gland in a 53?year?old man, which is incorrectly diagnosed as squamous cell carcinoma. Fine needle aspiration cytology(FNAC) smear obtained from the right parotid gland revealed scattered epithelial cell clusters or nests in a diffuse inflammatory and necrotic background. Some epithelial cells had squamoid appearance showing variable sized bizarre shaped nuclei. They had abundant of dense eosinophilic keratinized cytoplasm. Occasionally, parakeratotic cells were also present. These cytologic findings with significant atypia and necrotic background made diagnosis as squamous cell carcinoma. But, the resection specimen from this patient showed classic Warthin's tumor in addition to abundant areas of inflammation and squamous metaplasia. Metaplastic or infarcted Warthin's tumor in the salivary gland may be confused with false positive diagnosis of malignancy on FNAC. Therefore, cytopathologist should have adequate awareness of potential of erroneous diagnosis in FNAC of Warthin's tumor.
Biopsy, Fine-Needle* ; Carcinoma, Squamous Cell* ; Cytoplasm ; Diagnosis ; Eosinophils ; Epithelial Cells ; Humans ; Inflammation ; Metaplasia ; Parotid Gland ; Salivary Glands

Mucious cystic neoplasm of pancreas is a cystic neoplasm composed of columnar, mucin-producing epithelium and is supported by ovarian-type stroma. The key to the cytologic evaluation of pancreatic cystic lesions is to recognize the cytologic components as being diagnostic of a mucin-producing cystic neoplasm, as all of these neoplasms need to be resected. We report the use of fine needle aspiration cytology in the diagnosis of an invasive mucinous cystic carcinoma confirmed by partial pancreatectomy. The cytologic specimen showed a abundant mucin background and sheets or papillae of neoplastic cells. There are mucin-containing columnar cells that show a variable degree of cytologic atypia.
Biopsy, Fine-Needle* ; Diagnosis ; Epithelium ; Mucins* ; Pancreas* ; Pancreatectomy ; Pancreatic Cyst

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents a diverse spectrum of clinical presentation, morphology, and genetic and molecular alterations, and shows variable prognoses and responses to therapy. The International Prognosis Index (IPI) is widely used to predict prognosis but is not precise. METHODS: Thirty-nine cases of DLBCL were classified into low- and high-risk groups according to IPI and were analyzed for their p53, BCL-2, BCL-6 and PCNA expression profile by immunohistochemical staining and overall survival rate. RESULTS: The mean age of the 39 patients, 23 males and 16 females, was 52.6 years. There were 23 cases (59.0%) in the low-risk group and 16 (41.0%) in the high-risk group. p53, BCL-2, BCL-6 and PCNA expression was higher in the high-risk group than in the low-risk group, but only the differences in p53 and BCL-2 expression were statistically significant (p < 0.05). CONCLUSION: The p53 and BCL-2 protein expression in DLBCL may supplement IPI in predicting the prognosis of DLBCL patients.
B-Lymphocytes* ; Female ; Humans ; Lymphoma, B-Cell* ; Lymphoma, Large B-Cell, Diffuse ; Male ; Prognosis ; Proliferating Cell Nuclear Antigen* ; Survival Rate

Malignant fibrous histiocytoma (MFH) of the breast is extremely rare and most of the previous reports were focused on the clinicopathological features of breast MFH, so analysis of its imaging findings have been limited. We report a case of MFH involving left breast and left axilla, metastasized from known MFH of left forearm, with focusing on imaging findings based on radiologic evaluation of the breast including mammography, ultrasound and breast MRI.
Axilla ; Breast* ; Forearm ; Histiocytoma, Malignant Fibrous* ; Magnetic Resonance Imaging ; Ultrasonography, Mammary

PURPOSE: The expression of hormone receptors is the most reliable factor for predicting the responsiveness to hormonal therapy. At present, immunohistochemistry (IHC) is considered as a practically reliable method. This study was designed to examine the interlaboratory variance in immunohistochemical assays for estrogen receptor (ER) and progesterone receptor (PR) in Korea. METHODS: The Korean Study Group for Breast Pathology (KSGBP) made a questionnaire to know the current situation in HR assay in Korea. The questionnaire was sent to the members of KSGBP by e-mail, which were included eight questions relating to tissue handling, ER/PR IHC procedure and interpretation method. Forty laboratories replied with the completed questionnaire. RESULTS: All 40 laboratories were using formalin as a fixative. Pretreatment was performed using six different methods including autoclave (25%), microwave (30%) and full autostainer (15%). Primary antibodies for ER were SP1 in 40%, 6F11 in 27.5% and 1D5 in 32.5%. Primary antibodies for PR were more variable (seven clones) than those for ER. Interpretation method used was Allred system in 20%, modified Allred system in 15%, report the % of positive tumor cells in 45%, positive/ negative in 15% and others in 5%. The expression rate of ER was ranged from 45.6% to 93% (mean 63.5%) and the expression rate of PR was ranged from 27% to 90% (mean 59.1%). The differences according to the numbers of breast cancer in each institute, primary antibodies, detection systems and interpretation methods did not influence to the expression rate of ER/PR, statistically (p>0.05). CONCLUSION: In Korea, the interlaboratory variance in ER/PR IHC procedure was too huge to make a standardized method. We suggest the proper quality control program such as ER/PR staining with positive internal and external controls and negative control might be better to aim at getting similar results among the different laboratories rather than trying to standardize the procedure.
Antibodies ; Breast ; Breast Neoplasms ; Electronic Mail ; Estrogens ; Formaldehyde ; Handling (Psychology) ; Immunohistochemistry ; Korea ; Microwaves ; Progesterone ; Quality Control ; Receptors, Estrogen ; Receptors, Progesterone ; Surveys and Questionnaires