Gou Young Kim

Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer

The human beclin-1 gene, located on chromosome 17q21, has been identified as the mammalian orthologue of Atg6 (autophagy-related gene) and may be a haploinsufficient tumor suppressor gene. The function and expression of beclin-1 in human breast cancer are largely unknown. We investigated the expression of beclin-1 and bcl-2 in human breast cancer. Tissue samples from 125 cases of invasive breast cancer were used for the present study. Immunohistochemical staining for beclin-1 and bcl-2 was evaluated using tissue microarray, then the 2 proteins were correlated with clinicopathologic parameters. Positive beclin-1 expression and bcl-2 expression in breast cancer tissue were observed in 53 cases (42.4%) and 48 cases (38.4%), respectively. Beclin-1 expression was inversely correlated with bcl-2 expression in breast cancer tissue (P = .035). Beclin-1 expression significantly correlated with nuclear pleomorphism and mitotic count. Bcl-2 expression in breast cancer tissue significantly correlated with histologic grade, tubule formation, nuclear pleomorphism, mitotic count, estrogen receptor, and distant metastasis. Our results suggest that beclin-1 might play a role in the inhibition of the development of breast cancer and that inhibition might be due to an interaction with bcl-2 protein.

Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer

Cancer cells show a higher rate of anaerobic respiration than normal cells. The exact mechanisms for this higher glycolysis rate in cancer cells remain to be elucidated. The results of recent studies have indicated that p53, the most commonly mutated tumor suppressor gene, may have important functions in the regulation of energy-generating metabolic pathways that switch from oxidative phosphorylation to glycolysis via the synthesis of cytochrome c oxidase 2 (SCO2), p53-transactivated TP53-induced glycolysis (TIGAR), and apoptosis regulator. We evaluated the expression of p53, SCO2, TIGAR, and COX in 113 cases of invasive breast cancer using immunohistochemistry. A high expression of p53, SCO2, TIGAR, and COX was noted in 27.5% (31 cases), 84.1% (95 cases), 74.3% (84 cases), and 73.4% (83 cases) of the breast tumors, respectively. A high p53 expression was significantly associated with low expression levels of SCO2 (P = .008), COX (P < .0001), and TIGAR (P = .007). On the survival analysis, the low SCO2-expressing breast cancer patients showed a significantly poorer prognosis than that of the high SCO2-expressing breast cancer patients (P = .0078). These results suggest that p53 can modulate the metabolic pathways via the proteins SCO2 and TIGAR in human breast cancer.

Sonographic Findings of Ruptured Epidermal Inclusion Cysts in Superficial Soft Tissue Emphasis on Shapes, Pericystic Changes, and Pericystic Vascularity

The purpose of this study was to retrospectively evaluate the sonographic findings of ruptured epidermal inclusion cysts in superficial soft tissue, with an emphasis on shapes, pericystic changes, and pericystic vascularity.

Expression of HuR, COX-2, and survivin in lung cancers; cytoplasmic HuR stabilizes cyclooxygenase-2 in squamous cell carcinomas

Hu antigen R (HuR) is a member of the human family of embryonic-lethal, abnormal vision-like proteins, which serves as an mRNA-binding protein. In the cytoplasm, HuR can stabilize the mRNA of cyclooxygenase-2 (COX-2), an enzyme that catalyses the synthesis of prostaglandins and is associated with promotion of carcinogenesis and tumor cell resistance to apoptosis. Intracellular (cytoplasmic and nuclear) localization of survivin has a prognostic significance as an apoptosis inhibitor and a regulator of cell division in tumors. Patients with 151 squamous cell carcinomas and 93 adenocarcinomas underwent lobectomy or pneumonectomy with hilar and mediastinal lymph node sampling. Paraffin-embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin and HuR, and cytoplasmic staining of COX-2. In squamous cell carcinomas, COX-2 expression was correlated with a difference of survivin (cytoplasmic−nuclear; P=0.004), cytoplasmic HuR (P=0.018), total HuR (cytoplasmic+nuclear; P=0.009), and difference of HuR (P=0.020). COX-2 was inversely correlated with nuclear survivin (P=0.006). In a univariate analysis by log-rank test, survival was associated with cytoplasmic survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.005), difference of survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.014), and COX-2 (squamous cell carcinoma, P=0.001). Survival was inversely associated with nuclear survivin (adenocarcinoma, P=0.006, squamous cell carcinoma, P=0.014). In a multivariate survival analysis, cytoplasmic survivin (adenocarcinoma, P=0.002; squamous cell carcinoma, P=0.015) and COX-2 (squamous cell carcinoma, P=0.020) were determined as independent prognostic factors. Cytoplasmic HuR expression is associated with COX-2 expression in squamous cell carcinomas. The expression of COX-2 in squamous cell carcinomas, and cytoplasmic survivin in adenocarcinomas and squamous cell carcinomas could be useful independent prognostic markers.

Decreased Beclin-1 expression is correlated with the growth of the primary tumor in patients with squamous cell carcinoma and adenocarcinoma of the lung

Beclin-1 is a Bcl-2-interacting protein, and it may delay cell cycle progression and induce autophagy. The function and expression of Beclin-1 and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the lung remain largely unknown. Herein, we investigated the expression of Beclin-1 and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the lung. Tissue samples from 262 cases were used in this study. Immunohistochemical staining for Beclin-1 and Bcl-2 were conducted using a tissue microarray. In squamous cell carcinoma, Beclin-1 expression was strongly positive in 48 (28.6%) of 168 samples, it was moderately positive in 42 (25.0%) of 168 samples, and it was negative or weakly positive in 78 (46.4%) of 168 samples. In adenocarcinoma, Beclin-1 expression was strongly positive in 26 (27.7%) of 94 samples, it was moderately positive in 27 (28.7%) of 94 samples, and it was negative or weakly positive in 41 (43.6%) of 94 samples. Beclin-1 expression was inversely correlated with the tumor size and the primary tumor stage (pT) in both types of tumor. Especially, the TNM stage of adenocarcinoma was inversely correlated with Beclin-1 expression. Our results suggest that a progressively reduced Beclin-1 expression is correlated with the primary tumor growth of squamous cell carcinoma and adenocarcinoma of the lung.

Expression of the GLUT1 glucose transporter and p53 in carcinomas of the pancreatobiliary tract.

Only few studies have evaluated the usefulness of the GLUT1 and p53 status of pancreatobiliary tract carcinomas in revealing tumorigenesis. We studied GLUT1 and p53 immunoexpression in a total of 355 cases of the pancreatobiliary carcinoma to determine the biological significance of GLUT1 and p53 expression. Positive expression of GLUT1 was identified in 38 out of 67 (57.7%) ampulla of Vater (AV) carcinomas, in 27 out of 52 (51.8%) pancreatic (PA) carcinomas, in 38 out of 121 (31.4%) extrahepatic bile duct (EBD) carcinomas, and in 53 out of 115 (46.5%) gallbladder (GB) carcinomas. GLUT1 expression in pancreatobiliary carcinomas showed some positive correlation with histological grade, T stage, N stage, TNM stage, and lymphatic invasion. However, p53 expression showed no correlation with any prognostic factors. In the Kaplan-Meier test, positive GLUT1 expression was a poor prognostic factor in the pancreatobiliary tract cancers; however, only GB cancers were statistically significant (P=0.002). Our results suggest that GLUT1 expression in the AV, EBD, and GB carcinomas is associated with some prognostic factors, and GLUT1 expression is associated with a worse prognosis in the patients with GB carcinomas.

Loss of Raf-1 kinase inhibitory protein in pancreatic ductal adenocarcinoma

Aims: Raf‐1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers. The aim of this study was to evaluate RKIP expression and to determine its association with metastasis and prognostic significance in pancreatic cancer patients. Methods: Immunohistochemical staining for RKIP was performed on 63 cases of pancreatic ductal adenocarcinoma (PDAC). We investigated whether RKIP expression correlated with clinicopathological parameters and patient outcomes. Results: The islet cells, acinar cells and ductal epithelial cells of normal pancreas consistently showed strong RKIP immunoreactivity. In contrast, in PDAC, RKIP was lost in 57.1% (37/63) of cases. Loss of RKIP expression was significantly associated with the presence of nodal (p = 0.001) and distant (p = 0.010) metastases and a higher stage group (p = 0.012). Univariate analysis for distant metastasis‐free survival (DMFS) showed that the median DMFS of RKIP negative PDAC patients (10 months) was significantly shorter than that of RKIP positive PDAC patients (17 months; p = 0.009). Multivariate analysis also revealed that loss of RKIP expression was an independent predictor of worse DMFS in PDAC patients (p = 0.015). Conclusions: Our results strongly suggest that RKIP is a metastasis suppressor in PDAC.

Sonographic Findings of an Eccrine Spiradenoma : Case Report and Literature Review

An eccrine spiradenoma is a rare benign dermal tumor of the sweat gland. It is frequently solitary and presents as a small lesion (usually <1 cm) in the cutis and the subcutaneous tissue. 1 Because of its rare incidence and the lack of imaging workups for small superficial soft tissue nodules, few cases describing the imaging findings of an eccrine spiradenoma and other tumors of the sweat glands have been reported. We report the sonographic findings in a case of an eccrine spiradenoma that originated from the upper arm and discuss the previously reported imaging findings of sweat gland tumors.

Intrathyroidal branchial cleft-like cyst with heterotopic salivary gland-type tissue.

A rare case is described of intrathyroidal branchial cleft-like cyst associated with unusual heterotopic tissues including the salivary gland type tissue, fat, and cartilage. This coexistence in the thyroid gland has not been described previously, to our knowledge. The patient was a 7-year-old girl with a growing mass in the left lateral neck. The ultrasonography revealed a cystic lesion in the left thyroid. Histologically, the cyst was lined by squamous or respiratory-type epithelium resting on the fibrous tissue containing lymphoid tissues with follicle formation and solid cell nests (SCNs). This cyst was intimately associated with heterotopic tissues including lobules of well-differentiated seromucinous salivary glands, mature fat tissue, and islands of the cartilage. This association of branchial cleft-like cyst with SCNs and unusual heterotopic tissues in the normal thyroid suggests a possible origin from the SCN as ultimobranchial vestigial structures.

Stromal CD10 expression and relationship to the E-cadherin/β-catenin complex in breast carcinoma

Kim H‐S, Kim G Y, Kim Y W, Park Y‐K, Song J‐Y & Lim S‐J
(2010) Histopathology 56, 708–719
Stromal CD10 expression and relationship to the E‐cadherin/β‐catenin complex in breast carcinoma