Journal of Pathology and Translational Medicine

Volume 39(2); April 2005

Original Articles

S Phase Kinase Associated Protein 2 Expression in Breast Cancer and Its Prognostic Implications.: Eun Deok Chang, Eun Jung Lee, Se Jeong Oh, Chang Suk Kang; Korean J Pathol. 2005;39(2):69-73.

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Abstract PDF: BACKGROUND
S Phase Kinase Associated Protein 2 (Skp2), an F-box protein necessary for DNA replication, has recently been demonstrated to be an oncogene. The purpose of this study was to examine the Skp2 expression and to investigate its association with expressions of estrogen receptor (ER), androgen receptor (AR) and HER-2, as well as clinicopathological variables including tumor recurrence.
METHODS
The expressions of Skp2, ER and AR were examined by immunohistochemistry and HER-2 amplification by chromogenic in situ hybridization (CISH) in 117 cases of breast carcinoma.
RESULTS
Skp2 was expressed in 26 patients (22.2%) and was significantly correlated with tumor type (p=0.031), tumor grade (p=0.017) and ER expression (p=0.038). Twenty four (20.5%) of 117 patients had a tumor recurrence, and 6 patients (5.1%) died of multifocal metastases. Tumor recurrence was significantly correlated with histological grade (p=0.041) and lymph node status (p<0.001).
CONCLUSIONS
Although Skp2 expression was statistically insignificant in association with tumor recurrence, it might be useful as a biologic predictor in breast cancer. The simple and reliable immunohistochemical assay presented in this study can be a routine part of breast cancer evaluation and may influence patient management.

Expression of bcl-2, p53 and VEGF in Non-Small Cell Lung Carcinomas: Their Relation with the Microvascular Density and Prognosis.: Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2005;39(2):74-80.

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Abstract PDF: BACKGROUND
The aim of this study was to investigate the expression of bcl-2, p53 and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC), and to examine the relationship between those protein expressions and neovascularization. We also analyzed the prognostic impact of these biological parameters on the patients' overall survival rate.
METHODS
The archival tumor tissues from 147 previously untreated patients with NSCLC were examined by immunohistochemistry for bcl-2, p53 and VEGF proteins. The vascularity was measured by the average microvascular density (MVD) of the CD34-positive vessels. Clinical information was obtained through the computerized retrospective database from the tumor registry.
RESULTS
Immunoreactivity for bcl-2 was detected in 17% (25/147), p53 in 72% (106/147) and VEGF in 75% (110/147) of the tumors. An inverse association was found between bcl-2 expression and VEGF expression (p=0.012). There was a significant correlation between the bcl-2 expression and the MVD (p=0.009), and also between the p53 expression and the MVD (p=0.045). The mean survival time was associated with the patients' age (p=0.032), the T status (p=0.038), the tumor stage (p=0.009), and expressions of bcl-2 (p=0.016) and VEGF (p=0.039). On multivariate analysis, only the tumor stage and VEGF expression maintained their prognostic influence.
CONCLUSIONS
Our data suggest that bcl-2 and p53 alterations are involved in the angiogenesis of NSCLC, and are either dependent on or independent of VEGF. It is further noteworthy that the tumor stage and VEGF expression may be useful in predicting patients' survival.

Effect of Antenatal Dexamethasone Treatment on Neuronal Morphogenesis.: Soo Jeong Yoon, Heasoo Koo, Chong Il Kim; Korean J Pathol. 2005;39(2):81-90.

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Abstract PDF: BACKGROUND
Glucocorticoids (GCs) are essential for normal development and the maturation of the central nervous system. The aim of this study was to determine the effects of antenatal dexamethasone (DEXA) treatment on neuronal morphogenesis and on the glial cell line-derived neurotrophic factor (GDNF) protein expression in neonatal rat.
METHODS
Pregnant Sprague-Dawley rats were injected with saline (the control), or 0.2 mg/kg/day DEXA or 0.8 mg/kg/day DEXA at 17th, 18th and 19th day of gestation. The newborn rat brains were examined at postnatal days 1 (n=75) and 10 (n=78).
RESULTS
The DEXA-treated groups showed distorted architectures of neurons in the cerebral cortex, hippocampus and cerebellar cortex at postnatal days 1 and 10 with an increased number of proliferating cell nuclear antigen (PCNA)-positive cells. The cerebellar cortex in the DEXA-treated groups showed delayed development with more PCNA-positive cells in the internal granular cell layer. The Purkinje cells showed a markedly decreased number and the decreased length of the dendritic processes. The GDNF positive reaction was decreased in the DEXA-treated groups in a dose-dependent manner.
CONCLUSIONS
The developmental changes and neuronal degeneration at postnatal days 1 and 10 in the newborn rats that were exposed to DEXA at the late gestational age were associated with increased proliferative activity and a decreased level of GDNF protein expression.

Expression of p63,bcl-2,bcl-6 and p16 in Basal Cell Carcinoma and Squamous Cell Carcinoma of the Skin.: Zhenlong Zheng, Youngchul Kye, Xianglan Zhang, Aeree Kim, Insun Kim; Korean J Pathol. 2005;39(2):91-98.

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Abstract PDF: BACKGROUND
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the common malignant neoplasms of the skin. The p63 is a p53 homologue which is considered to be a reliable keratinocyte stem cell marker. Bcl-2 plays a key role in cell longevity by preventing apoptosis, whereas the bcl-6 gene functions as a transcriptional repressor. The p16-CDK4/6 complex arrests the cell cycle at G0 /G1 phase. In the present study, the expression of p63, bcl-2, bcl-6, and p16 in BCC and SCC was evaluated.
METHODS
Forty-seven BCCs and 43 SCCs were selected and microarrayed in paraffin blocks. Immunohistochemical analysis was performed with specific antibodies for bcl-2, bcl-6, p16 and p63.
RESULTS
p63 was found to be expressed in all BCCs and SCCs. Bcl-2 was exclusively expressed in BCCs (100%), but there was negative expression in SCCs, whereas bcl-6 was positively expressed in 18.2% of SCCs, and was negative in BCCs. In SCCs, p16 was expressed at high frequency (47.7%) than in BCCs (14.9%). The expression of p16 was correlated with the histologic grades of SCCs.
CONCLUSION
The different patterns of bcl-2, bcl-6, p63 and p16 protein expression between BCCs and SCCs may represent the different histogenesis and morphologic features of two lesions.

Expression of Vascular Endothelial Growth Factors A,C and D in Gastric Adenocarcinoma.: Myoung Ja Chung, Jin Wook Lee, Ki Hoon Yu, Doo Hyun Yang, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 2005;39(2):99-105.

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Abstract PDF: BACKGROUND
Vascular endothelial growth factor (VEGF)-C and VEGF-D are novel growth factors that regulate lymphatic vessel growth. This study was designed to examine whether the expression of three VEGF family members, VEGF-A, VEGF-C and VEGF-D are associated with the clinicopathologic parameters, especially with lymph node metastasis, in advanced gastric carcinomas.
METHODS
Immunohistochemical staining was performed for VEGF-A, VEGF-C, and VEGF-D in the surgically resected specimens from 102 patients with advanced gastric carcinoma. The mRNA expressions of the three VEGF family members were assessed in 16 cases of tumor tissues and their corresponding non-neoplastic tissues.
RESULTS
Of the 102 gastric carcinomas, 74 (73%), 82 (80%), and 34 (33%) cases showed cytoplasmic immunoreactivity for VEGF-A, VEGF-C and VEGF-D, respectively. Both VEGF-A and VEGF-C expressions were associated with lymphatic invasion and lymph node metastasis (p<0.05), but the VEGF-D expression was not associated with them (p>0.05). In the tumor tissue, VEGF-C mRNA expression was greater, while VEGF-D mRNA expression was lower than in the nonneoplatic tissue adjacent to the tumor.
CONCLUSIONS
VEGF-A and VEGF-C may play important roles for the lymphatic spread of gastric carcinoma. We suggest that neutralizing both VEGF-A and VEGF-C may be reguired to block lymph node metastasis.

A Standardized Pathology Report for Gastric Cancer.: Woo Ho Kim, Cheol Keun Park, Young Bae Kim, Youn Wha Kim, Ho Guen Kim, Han Ik Bae, Kyu Sang Song, Hee Kyung Chang, Hee Jin Chang, Yang Seok Chae; Korean J Pathol. 2005;39(2):106-113.

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Abstract PDF: BACKGROUND
AND METHODS: The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists developed a standardized pathology reporting format for gastric cancer in collaboration with the Korean Gastric Cancer Association. RESULTS: The diagnostic parameters are divided into two part: the standard part and the optional part. The standard part contains most of the items listed in the Japanese classification, the TNM classification by UICC, the WHO classification, and the Korean Gastric Cancer Association classification. Therefore, the standard part is adequate for routine surgical pathology service. We included detailed descriptions on each item.
CONCLUSIONS
The authors anticipate that this standardization can improve the diagnostic accuracy and decrease the discrepancies that occur in the pathologic diagnosis of gastric cancer. Furthermore, the standard format can encourage large scale multi-institutional collaborative studies.

Prognostic Significance of Abnormal beta - catenin Expression in Breast Carcinoma.: Won Ae Lee; Korean J Pathol. 2005;39(2):114-119.

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Abstract PDF: BACKGROUND
The subcellular localization and activity of beta-catenin are tightly regulated within the cell. The aim of this study was to analyze the aberrant beta-catenin expression in breast carcinomas and to determine its clinical significance.
METHODS
Fifty five cases of breast carcinoma were immunostained with monoclonal antibodies against beta-catenin. Normal expression of -catenin was defined as exclusive membranous staining. Abnormal expression of beta-catenin was reclassified into 3 categories: complete or partial loss of membranous staining (LOM) without cytoplasmic staining and nuclear staining, LOM with cytoplasmic staining and without nuclear staining, and LOM with nuclear staining and with/without cytoplasmic staining. RESULTS: Normal membranous beta-catenin expression was detected in 25 (45.5%) of 55 cases of breast carcinoma. Thirty cases with abnormal -catenin expression comprised 9 cases (16.1%) showing LOM without cytoplasmic and/or nuclear staining, 20 cases (36.4%) showing LOM with cytoplasmic staining and without nuclear staining, and one case (1.8%) showing LOM with nuclear and cytoplasmic staining. Abnormal beta-catenin expression was significantly correlated with lymph node metastasis (p=0.03). LOM with cytoplasmic and/or nuclear expression was significantly correlated with poor disease free survival by univariate (p=0.03) and multivariate analyses (p=0.03). In addition, it was correlated with poor overall survival with a borderline significance (p=0.059).
CONCLUSIONS
This study suggests that the cytoplasmic and/or nuclear expression of beta-catenin can be used as a biologic marker for predicting disease recurrence and poor patients' survival in breast carcinomas.

Case Reports

Ependymoma Arising from the Pelvis: A Case Report.: Kyungji Lee, Jihan Jung, Youn Soo Lee, Kyo Young Lee, Byung Kee Kim, Chang Suk Kang; Korean J Pathol. 2005;39(2):120-124.

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Abstract PDF: We report here on a case of an ependymoma arising from the pelvis in a 25-year-old woman. She had no evidence of abnormality in her brain and bilateral ovaries. The diagnosis was based on light microscopic, immunohistochemical, and ultrastructural features of a typical ependymoma, including the patterns of pseudorosette or true ependymal rosette, the strong immunopositivity for glial fibrillary acid protein and intermediate filaments, and cilia of tumor cells. The mass was over 20 cm in maximum diameter, and it was located between the uterus and rectum without any connection to bilateral ovaries. There were many metastatic nodules in the pelvis and omentum. In addition, the proliferation index in the most active area was 10% by immunohistochemistry using monoclonal antibody MIB-1. Although the prognosis of the pelvic ependymoma is known to be difficult to evaluate, this case may serve to illustrate the poor prognostic course, according to the size of the tumor, the evidence of metastasis, and the MIB-1 labelling index.

A Case of Combined Hepatocellular and Cholangiocarcinoma with Neuroendocrine Differentiation and Sarcomatoid Transformation: A Case Report.: Mi Jung Kim, Hyun Lyoung Koo, Seung Kyu Lee, Jae Y Ro, Eunsil Yu; Korean J Pathol. 2005;39(2):125-129.

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Abstract PDF: We report here on a case of combined hepatocellular and cholangiocarcinoma (CHC) with neuroendocrine differentiation and sarcomatoid transformation. A 59-year-old male who had had HBV-associated chronic liver disease presented with hepatic masses. The explanted liver showed three small masses, two in the right lobe and one in the left lobe. The largest one in the right lobe was a 2.0 cm sized binodular mass,consisting of a yellowish tan nodule and an abutting reddish brown nodule. Microscopically, the reddish brown nodule was a cholangiocarcinoma (CC) showing neuroendocrine differentiation and sarcomatoid tranformation. The yellowish tan nodule and the remaining two masses were hepatocellular carcinoma (HCC)s. On immunohistochemistry, both the adenocarcinoma and spindle sarcomatoid cells were positive for pancytokeratin, but only the adenocarcinoma cells were positive for chromogranin and carcinoembryonic antigen (CEA). Mitotic and Ki67 labeling indices as well as p53 immunopositivity were significantly increased only in the CC component. We report here on the first case of CHC in which the CC displayed neuroendocrine differentiation and sarcomatoid transformation with high mitotic and Ki67-labeling indices, as well as having p53 overexpression.

Epithelioid Myofibroblastoma of Mammary-type in Chest Wall: A Case Report.: Hyun Jung Kim, Hunkyung Lee, Ok Jun Lee, Kyung Ja Cho, Jae Y Ro; Korean J Pathol. 2005;39(2):130-133.

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Abstract PDF: Mammary-type myofibroblastoma of the soft tissue is a benign mesenchymal tumor, and it is a recently established clinical entity. We report a case of myofibroblastoma of the chest wall with a prominent epithelioid feature, that occurred in a 12-year old female. Although the lesion occurred in the breast area, there was no breast parenchyma in or around the mass, which favored soft tissue of the chest wall origin. The tumor was immunohistochemically identical to the mammary-type myofibroblastoma with diffuse and strong positivity against CD34 and desmin. The myoepithelial differentiation of the tumor was further supported by the electron microscopic analysis. This case indicates that mammary-type myofibroblastoma can occur in a young girl. The mammary-type myofibroblastoma should be considered a differential diagnosis, among epithelioid soft tissue neoplasms in the chest wall when the proper immunohistochemical work-up is done.

Invasive Ductal Carcinoma Arising in a Recurrent Malignant Phyllodes Tumor: A Case Report.: Ahwon Lee, Gyeongsin Park, Kyo Young Lee, Chang Suk Kang, Byung Kee Kim, Sang In Shim; Korean J Pathol. 2005;39(2):134-136.

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Abstract PDF: 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.

Fibromatosis of the Breast: A Case Report.: Hyun Joong Kim, Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Ji Shin Lee, Chan Choi; Korean J Pathol. 2005;39(2):137-139.

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Abstract PDF: Fibromatosis of the breast is a rare tumor. We describe here a case of mammary fibromatosis in a 37-year-old woman. The mass from the right breast was 3 cm at the greatest dimension. The lesion was poorly circumscribed, firm and white-gray on the cut surface. Histologically, the lesion infiltrated into the lobules of the breast, and the tumor was composed of relatively uniform fibroblasts and collagen. Neither mitotic activity nor cellular atypia was seen. On the immunohistochemistry, the cells were positive for vimentin and they were focally positive for smooth muscle actin. Staining results for estrogen receptor and progesterone receptor were negative.

Actinomycosis of the Intrahepatic Bile Duct, Superimposed on Hepatolithiasis: A Case Report.: Ji Han Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2005;39(2):140-144.

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Abstract PDF: Actinomycosis is a chronic suppurative infection caused by Actinomyces, a filamentous, grampositive, anaerobic bacterium that is a normal inhabitant of the oral cavity and gastrointestinal tract. Actinomycosis of the biliary duct is very rare and the pathogenesis of this infection is poorly understood. We report here on a case of actinomycosis in the intrahepatic bile duct that was superimposed on hepatolithiasis. A 55-year-old woman presented with epigastric discomfort and episodic upper abdominal pain for 1 year. The radiologic findings revealed multiple hepatolithiasis and cholelithiasis. On performing left lateral segmentectomy of the liver, the markedly dilated intrahepatic bile duct contained several brown pigmented stones, and periductal chronic inflammation with fibrosis and proliferation of the bile ductules were observed. In addition to the intrahepatic stones, there were sulfur granules with neutrophilic infiltration and necrotic debris. The gram stain and methenamine silver stain revealed tangled filamentous and branching bacteria, which were consistent with Actinomyces. Acid-fast staining result was negative and no malignancy was detected.

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