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: About 10% of high-grade squamous intraepithelial lesions (HSILs) progress to invasive carcinomas within 2-10 years. By delineating the events that occur in the early stage of the invasion, the pathogenesis of cervical cancer could be better understood. This will also propose the possible methods for inhibiting the tumor invasion and improving the survival of patients. METHODS: We compared the genomic profiles between the HSIL and the invasive squamous cell carcinoma (SCC) using an array comparative genomic hybridization. Using recurrently altered genes, we performed a principal component analysis to see variation of samples in both groups. To find possibly affected pathways by altered genes, we analyzed genomic profiles with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and GOEAST software. RESULTS: We found 11q12.3 and 2p24.1 regions have recurrent copy number gains in both groups. 16p12-13 and 20q11-13 regions showed an increased copy number only in cases of HSIL. 1q25.3 and 3q23-29 regions showed copy number gains only in cases of SCC. Altered genes in the SCC group were related to the mitogen-activated protein kinase signaling pathway and the RNA transport. Altered genes in the HSIL group were related to the ubiquitin mediated proteolysis and cell adhesion molecules. CONCLUSIONS: Our results showed not only that gains in 11q12.3 and 2p24.1 were early events occurring in the premalignant lesions and then maintained in cases of SCC but also that gains in 1q25.3 and 3q23-29 were late events occurring after invasion in those of SCC.
Carcinoma, Squamous Cell ; Cell Adhesion ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Coat Protein Complex I ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Female ; Gene Dosage ; Genome ; Principal Component Analysis ; Protein Kinases ; Proteolysis ; RNA Transport ; Ubiquitin ; Uterine Cervical Neoplasms

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

We report here on a case of invasive ductal carcinoma arising in a recurrent malignant phyllodes tumor. The patient was a 33-year-old woman who presented with a left breast mass, and an excision was then performed. The mass, measuring 7.0 x 4.0 cm in size, was relatively well demarcated with a nodular contour and showed pale gray and solid cut surface with clefts on it. Histologically, the mass mainly consisted of stromal components that were characterized by high cellularity, marked nuclear atypism and brisk mitosis. The sparse glandular components were leaf-like in shape and lined by bland ductal epithelium without any nuclear atypism. Sixteen months later, the patient revisited our hospital with a recurrent mass, and underwent total mastectomy. The recurrent mass contained foci of definite invasive ductal carcinoma in the background of malignant phyllodes tumor, which was identical to the primary mass. This case demonstrates that it is possible that an invasive ductal carcinoma might arise within, at least with, a recurrent malignant phyllodes tumor.
Adult ; Breast ; Carcinoma, Ductal* ; Epithelium ; Female ; Humans ; Mastectomy, Simple ; Mitosis ; Phyllodes Tumor*