Journal of Pathology and Translational Medicine

Volume 39(6); December 2005

Original Articles

Bioethical Review on the Use of Human Tissue.: In Hoe Ku; Korean J Pathol. 2005;39(6):365-371.

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Abstract PDF: Hospitals and medical research institutions have vast holdings of tissues stored in tissue banks. Tissue can end up in a tissue bank for many different reasons. Tissue samples are taken as part of normal diagnostic procedures, and the remaining samples after analysis may be stored for secondary analysis to confirm the diagnosis, for quality control or for research purposes. If the tissues have been stored properly, in principle, it is possible to perform almost all the genetic tests. This opens up possibilities for an expanded use of such tissues in medical research, and therefore tissue banks have become scientifically and economically valuable resources. New genetic testing technologies with their scientific and economic potential are raising ethical concerns about the use of older, stored tissue samples, in particular those that were obtained for one purpose and can now be used for other purposes. Much of these tissues was obtained without consent or with a consent that does not cover genetic testing. There are no general ethical guidelines that can decide whether a specific research project is justifiable. In some cases, proxy consent or an analysis of ownership may be useful. However, use of tissue samples, in most cases, will depend on whether the project is worthwhile and ethically acceptable according to today's standards.

Management and Ethics of Biobank; Biorepository.: Bong Kyung Shin, Jung Woo Choi, Hyunjuu Lee, Aree Kim, Insun Kim, Han Kyeom Kim; Korean J Pathol. 2005;39(6):372-378.

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Abstract PDF: Research access to a large number of high-quality biospecimen, adequately annotated and ethically acquired, is critical to an improved understanding of disease and ultimately new development of effective diagnostic markers and therapeutic targets. Therefore, the importance of biobanking is widely recognized within the life science and healthcare communities. Resolution of the ethical issues, including informed consent, confidentiality and institutional review board approval, are probably the most important task to every biobank or biorepository. In Korea, the new, very strict ethical act on research, issued in 2005, requires researchers as well as biorepositories to know how they use or run a biorepository ethically without damaging the right of human subjects who gave the repository their biospecimen.

The Status of Pathology Specimen Bank in Other Countries.: Han Ik Bae, Ghil Suk Yoon; Korean J Pathol. 2005;39(6):379-383.

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Abstract PDF: Pathology specimen has been collected for purposes of education and research, particularly with respect to basic, developmental and translational studies in many areas of cancer research including molecular biology, immunology, and genetics. Even though no policy or ethical guideline drafted to regulate research tissue bank in Korea, advanced countries has been concerned ethical issues in the collections, storages, specimen transports and informatics for pathology specimen bank. Informed consent and confidentiality for protection of personal data records, which can be directly or indirectly associated with linked data from the donors' point of view, are the key to banking all over the world. The institutional review board (IRB) is important to ensure the scientific and ethical quality of pathologic specimen research. Increasing molecular genetic testing is also resulting in an increased demand of quality control for high quality nucleic acids. Most recently, the use of stored human tissue for education and research has become an object of increased ethical concern in Korea. Korean Association of Pathologists (KAP) has in urgent need of the policies and a standardized operating procedure, regulating a good collection practice of pathology specimen bank.

Expression of Epidermal Growth Factor Receptor Related Protein in Gallbladder Cancer: An Association with p53 Mutation.: Ho Sung Park, Kyu Yun Jang, Kyung Ryoul Kim, Hak Yong Lee, Andrzej S Tarnawski, Adhip P N Majumdar, Myoung Jae Kang, Dong Geun Lee, Woo Sung Moon; Korean J Pathol. 2005;39(6):385-390.

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Abstract PDF: BACKGROUND
It has been well demonstrated that the overexpression of epidermal growth factor receptor (EGFR) is associated with numerous gastrointestinal malignancies, including gallbladder carcinoma. However, the cellular events that regulate EGFR in cancer cells have not been fully elucidated. A novel negative regulator of EGFR that is referred to as EGFR related protein (ERRP) has recently been identified. The aim of this study was to investigate the expression and localization of ERRP in gallbladder carcinoma and to examine a possible role for ERRP.
METHODS
We examined the immunohistochemical expressions of ERRP, p53 and proliferating cell nuclear antigen labeling index (PCNA-LI) in formalin-fixed, paraffinembedded specimens of 43 cases of gallbladder carcinoma, 7 cases of adenoma and 3 cases of dysplasia.
RESULTS
In the normal mucosa, ERRP immunoreactivity was positive in over 64% of specimens. In contrast, the ERRP staining was positive in only 46% of the cancer specimens. The expression of ERRP in cancer cells was inversely correlated with tumor cell proliferation. The loss of ERRP expression correlated with the p53 overexpression.
CONCLUSIONS
Our data indicate that the down-regulation or loss of ERRP could play an important role in the progression of gallbladder carcinoma. The inverse relationship between the ERRP expression and PCNA-LI suggests that ERRP may play a role in the inhibition of tumor cell proliferation in gallbladder cancer.

Expression of p34(cdc2), p27(Kip1), p21(WAF1/Cip1) and p53 in Human Breast Cancers.: Dong Hoon Kim, Chan Kum Park, Ho Jung Lee, Won Mi Lee, Eun Kyung Kim, Jong Eun Joo; Korean J Pathol. 2005;39(6):391-400.

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Abstract PDF: BACKGROUND
Cell cycle progression is governed by cell cycle regulators and inhibitors such as the cyclin dependent kinases (CDK), p27(Kip1), p21(WAF1/Cip1) and p53. The purpose of this study was to correlate expressions of p34(cdc2), p27(Kip1), p21(WAF1/Cip1) and p53 with the various clinicopathologic prognostic parameters of human breast cancers.
METHODS
The paraffin-embedded tissue sections from 102 patients with human breast carcinomas were examined by performing immunohistochemical staining. The primary antibodies used for immunohistochemical staining were mouse monoclonal antibody to human p34(cdc2), p27(Kip1), p21(WAF1/Cip1), p53, ER and PR.
RESULTS
The expression rates of p34(cdc2), p21(WAF1/Cip1) and p53 were 29.3%, 40.2% and 49.1% in breast carcinomas, respectively. In normal breast tissues, p34(cdc2), p21(WAF1/Cip1) and p53 were not expressed. The p34(cdc2) was expressed in the cytoplasm of cancer cells. The expression rate of p27(Kip1) was 29.3% in breast carcinomas and 100% in normal breast tissues, so the loss of p27(Kip1) expression in breast cancer was noted. The high expression of p21(WAF1/Cip1) in neoplastic cells was associated with the p53 expression (p=0.03). The expression of p27(Kip1) was correlated with that of the progesterone receptor (PR) (p=0.04) and the expression of p21(WAF1/Cip1) was correlated with that of positivity for estrogen receptor (ER) (p=0.04) and PR (p=0.04). No correlation was demonstrated between the mean patient survival and the expression rate of p34(cdc2), p27(Kip1), p21(WAF1/Cip1) and p53.
CONCLUSIONS
The loss of the normal cell growth cycle by the abnormal expression of cyclin dependent kinases and their inhibitors and the steroid hormones may play an important role in human breast carcinogenesis. The p53 dependent p21(WAF1/Cip1) pathway, the p27(Kip1) protein loss and the cdc2 overexpression were important in development and progression of human breast cancer.

Expression of Vascular Endothelial Growth Factor-C in Breast Carcinoma.: Myoung Ja Chung, Sun Ho Yang, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 2005;39(6):401-405.

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Abstract PDF: BACKGROUND
Vascular endothelial growth factor-C (VEGF-C) is a novel growth factor that regulates lymphangiogenesis and/or angiogenesis via binding to the vascular endothelial growth factor receptor-3 (VEGFR-3) or VEGFR-2. Recent studies have suggested that VEGF-C may play a role in lymph node metastasis. This study was conducted to examine whether the expression of VEGF-C is associated with the clinicopathologic parameters, and especially lymph node metastasis, of invasive ductal carcinoma.
METHODS
Immunohistochemical staining was performed for VEGF-C and CD31 in the surgically resected specimens from 83 patients with invasive breast carcinoma.
RESULTS
Of the 83 breast carcinomas, 61 (74%) cases showed cytoplasmic VEGF-C imunoreactivity. VEGF-C expression was associated with lymph node metastasis (p=0.03), but it did not correlate with tumor size, the histologic grade, and the presence of estrogen receptor or progesteron receptor. The mean microvessel density in the cases without VEGF-C expression was 51.9+/-30.1 and it was 72.9+/-33.0 in the cases with 2+ expression for VEGF-C (p=0.07).
CONCLUSIONS
This study suggests that VEGF-C expression may have an association with lymph node metastasis in the patients with breast carcinoma.

Renal Cell Carcinoma Associated with Xp11.2 Translocation: Clinicopathologic and Immunohistochemical Findings of 4 Cases.: Sanghui Park, Ji Eun Kwon, Yeon Lim Suh; Korean J Pathol. 2005;39(6):406-411.

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Abstract PDF: BACKGROUND
The new WHO classification includes the recently described renal cell carcinomas (RCC) that are associated with several different translocations, involving chromosome Xp11.2, and they all result in gene fusions involving the TFE3 gene. The authors describe the clinicopathologic and immunohistochemical findings of 4 patients who had the morphologic features of RCC with Xp11.2 translocations.
METHODS
Among 9 surgically resected and pathologically proven pediatric RCCs, 4 showed a typical RCC histopathology with the Xp11.2 translocation. Immunohistochemical stains were performed for TFE3, AE1/AE3, epithelial membrane antigen, vimentin, HMB45, S-100 protein and CD10.
RESULTS
The 4 study subjects included one male and 3 females, and their chief complaints were gross hematuria and abdominal pain. Histologically, the tumors showed two different histologic types: type 1 tumors (2 cases) that corresponded to those of ASPL-TFE3 RCC, and type 2 tumors (2 cases) that corresponded to PRCC-TFE3 RCC. Nuclear TFE3 immunostaining was seen in 3 cases. All the tumors were immunoreactive for CD10, and vimentin and cytokeratin were expressed in 3 cases and HMB-45 was expressed in 2 cases.
CONCLUSIONS
Our results show that significant numbers of pediatric RCC are translocation-related. Therefore, when one encounters an RCC in the pediatric population, the possibility of a translocation-related RCC should be kept in mind.

Expression of Thymidylate Synthase in Non-Small Cell Lung Cancer.: Jinyoung Yoo, Suzi Kim, Byoung Yong Shim, Sung Hwan Kim, So Hyang Song, Deog Gon Cho, Meyung Im Ahn, Chi Hong Kim, Kyu Do Cho, Seok Jin Kang, Hoon Kyo Kim; Korean J Pathol. 2005;39(6):412-417.

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Abstract PDF: BACKGROUND
Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), and this is an essential step in DNA biosynthesis. The present investigation was designed to determine the expression of TS in the patients with non-small cell lung cancer (NSCLC) and to assess the possible associations between the TS status and the p53 or proliferative index (PI).
METHODS
The archival tumor tissues from 56 previously untreated NSCLC patients were examined by immunohistochemistry for TS, p53 and Ki-67.
RESULTS
Forty-one men and 15 women (age range: 35 to 79 years, mean age: 62 years) were included in this study. The TS expression was high in 40 patients (71.4%) and low in 16 patients (28.6%). The aberrant expression of p53 was detected in 35 patients (62.5%). The mean PI for all the patients was 31.4+/-12.1. The TS-high tumors tended to be more poorly differentiated (p=0.069). The TS expression by a semiquantitative fourscale grading system was significantly correlated with the PIs (p=0.003). No correlation was established between the TS expression and the p53 status (p=0.806) or survival (p=0.951). CONCLUSIONS: TS was not confirmed to be a useful marker for determining the prognosis of NSCLC patients. However, our data suggest that the tumor cells with higher TS expression have a higher proliferative activity.

The Expression of Matrix Metalloproteinase-9 and Tumor Angiogenesis in Human Osteosarcoma.: Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Anhi Lee, Eun Joo Seo, Sang In Shim, Chang Suk Kang; Korean J Pathol. 2005;39(6):418-423.

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Abstract PDF: BACKGROUND
Matrix metalloproteinase-9 (MMP-9) is a matrix-degrading enzyme that's believed to play a crucial role not only for tumor invasion and metastasis, but also for a variety of stromal reactions, including neovascularization. The aim of this study was to investigate the expression of MMP-9 and to compare its expression with the angiogenesis activity in human osteosarcoma.
METHODS
Archival tumor tissue samples from 20 patients with osteosarcoma were analyzed by performing immunohistochemistry for the expression of MMP-9 and CD34. The vascularity was measured as the average microvascular density (MVD) of the CD34-positive vessels. The clinical information was obtained through searching the computerized retrospective database from the tumor registry.
RESULTS
MMP-9 was expressed in 90% (18/20) of the tumors we examined. The MVD ranged from 10.5 to 179.7 with a mean of 64.9. There was no significant correlation between the MMP-9 expression and the MVD (p=.613). The MMP-9 expression was not associated with any of the clinicopathologic variables, whereas the MVD showed an increasing tendency according to the metastasis status (p=.073).
CONCLUSIONS
We demonstrated that MMP-9 activation is likely to occur in human osteosarcoma. However, there was no direct involvement of MMP-9 with tumor angiogenesis. It is noteworthy that MVD may aid physicians to predict the presence of distant metastasis in osteosarcoma patients.

Case Report

Peripheral Micronodular Squamous Cell Carcinoma of the Lung Unexpectedly Discovered after an Operation for Spontaneous Pneumothorax: A Case Report.: Hyoun Wook Lee, Phil Jo Choi, Mee Sook Roh; Korean J Pathol. 2005;39(6):424-427.

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Abstract PDF: The occurrence of lung cancer in patients suffering with pneumothorax is very rare, especially in the absence of any radiological changes that would suggest neoplasia after the pulmonary reexpansion. We have experienced a case of a 60-year-old male who presented with lung cancer that was discovered by chance after an operation for his pneumothorax. The resected lung tissue showed a 0.3 cm-sized, peripheral squamous cell carcinoma associated with a bulla. The tumor was not macroscopically detected on the first thoracotomy that was performed for the treatment of the pneumothorax. The micronodular cancer was diagnosed after the histological examination of the resected bulla. The patient has been doing well with no evidence of tumor recurrence during the fifteen months follow-up. This case shows that we should always be vigilant for associated lung cancer when we examine the lung tissue after the operation for pneumotherax.

Original Article

Gangliocytic Paraganglioma.: Joon Mee Kim, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Young Chae Chu, Hyung Gil Kim, Sun Geun Choi; Korean J Pathol. 2005;39(6):428-432.

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Abstract PDF: Gangliocytic paraganglioma (GP) is a rare benign tumor that is usually seen in the duodenum. It shows unique histologic features that are composed of a carcinoid or paraganglioma-like appearance, ganglion cells, and Schwann cells. The common presenting symptoms are abdominal pain, gastrointestinal bleeding and obstruction. The lesion can sometimes be asymptomatic and they are discovered incidentally. We experienced a case of incidentally found GP in a 73 year-old-man who had a colon cancer with liver metastasis. During the preoperative workup, a submucosal tumor was found in the duodenal papilla. The frozen diagnosis of the duodenal mass was GP, which was confirmed by the permanent sections and immunohistochemical staining. Pathologists should be alert to recognize and diagnose this rare, but benign disease, especially in the patient suffering with gastrointestinal cancer.

Case Reports

Papillary Cystadenocarcinoma In The Retromolar Area: A Brief Case Report.: Dongchul Kim; Korean J Pathol. 2005;39(6):433-436.

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Abstract PDF: Salivary gland papillary cystadenocarcinomas are rare lesions, and particularly when they are found in the oral cavity. They have been recognized as being low grade carcinomas of the salivary glands. The author reports here on a case of recurrent papillary cystadenocarcinoma in the right retromolar area. The initial mass had multicystic and papillary structures with low grade features. The recurred mass showed basically the same histologic features. However the layer of papillae and the solid portion were increased and the tumor cells were larger and more pleomorphic with prominent nucleoli and frequent mitoses. Focal comedo type tumor necrosis and spindle cell proliferations in the surrounding soft tissue were present. This is a very rare report of a minor salivary gland papillary cystadenocarcinoma in a Korean, and the morphologic dedifferentiation was accompanied by the clinical recurrence.

Epithelial Cysts in the Intrapancreatic Accessory Spleen that Clinically Mimic Pancreatic Cystic Tumor: A Report of Two Cases.: Jae Kyung Won, You Jeong Lee, Gyeong Hoon Kang; Korean J Pathol. 2005;39(6):437-441.

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Abstract PDF: Cystic lesions in the accessory spleen are extremely rare and they present a challenging clinical differential diagnosis. We report here on two cases of epithelial cyst of intrapancreatic accessory spleen that mimicked pancreatic cystic tumor. In both cases, the patients underwent distal pancreatectomy under the impression of a benign cystic tumor of the pancreas. Unilocular or multilocular cysts in the pancreas tail were observed, and these were later shown to be epithelial cysts in the accessory spleen located within the pancreatic tail. The cysts were lined by columnar, cuboidal or stratified squamous epithelium.

Editorial

Why and How to Use Surgical Pathology Terminology in Korean?.: Je G Chi; Korean J Pathol. 2005;39(6):442-444.

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Abstract PDF: The great majority of the terms that are used in describing the pathological findings are in English. These English terms became very familiar to most surgical pathologists in non-English speaking countries including Korea. Considering the situation of global importance of diagnostic pathology for the better international communication. It is acceptable to our Korean pathologists to be competent in English and English terminology. However, it is equally important to be competent and fluent in Korean terminology as well. Therefore, instead of mixing or combining two languages in describing pathological changes, it should be encouraged to be competent in both Korea and English. The author proposes a list of Korean terms that could best fit for the corresponding English terms that are frequently used in describing gross and microscopic findings in routine surgical pathology. It is hoped that these proposed terms could be standardized through the process of feedback from the members of our Society, and be used routinely in everyday practice.

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