Journal of Pathology and Translational Medicine

Volume 35(3); June 2001

Original Articles

Absence of TaqI Polymorphism in Exons of Complement Component C9 Gene in Koreans.: Seoyoung Han, Sang Ho Kim; Korean J Pathol. 2001;35(3):185-188.

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Abstract PDF: BACKGROUND
Molecular and genetic studies of the complement component C9 have never been reported in Korea.
METHODS
We have checked the TaqI polymorphism of the C9 gene in 52 randomly selected adult Koreans. Southern blot analysis was carried out to detect the restriction fragment length polymorphism (RFLP) of the C9 gene. The fragments of human C9 cDNA were hybridized with the TaqI digested genomic DNA.
RESULTS
The functional levels of complements in all subjects were measured at 84.4+/-3.8% by hemolytic assay, which indicates that the subjects have functionally normal complement systems. Fifty-four percent of the individuals were found to have the C9 genes that contain the constant fragments only. It seems that the undetected TaqI site may be located in the intron of the C9 gene. The silent mutation of C->T transversion was found in exon 1 of the C9 gene through polymerase chain reaction-single strand conformational polymorphism, but no mutation was found in exon 4 of the C9 gene.
CONCLUSIONS
We could not find TaqI polymorphism in exons of the C9 gene in 52 Koreans.

Cardiac Myocyte Cell Death in Isoproterenol-Induced Cardiac Hypertrophy in Rats.: Soo Kyung Kim, Eun Sook Chang, Gee Youn Kwon; Korean J Pathol. 2001;35(3):189-195.

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Abstract PDF: BACKGROUND
Although cardiac hypertrophy contributes to cardiac failure, the underlying mechanism has not yet been precisely determined. This study was planned in order to determine the pathogenesis of heart failure following cardiac hypertrophy induced by -adrenergic stimulation.
METHODS
The extent of cardiac hypertrophy was assessed after administrating isoproterenol (ISO, 5 mg/kg) intraperitoneally for 6 hours, 1, 3, 5, 7 and 10 days. The hematoxylin-eosin, Masson's trichrome and phosphotungstic acid hematoxylin stains along with immunohistochemical stainings for proliferating cell nuclear antigen and Ki-67 were performed in the paraffin-embedded left ventricle sections. Apoptosis was assessed by DNA laddering and terminal deoxynucleotidyl transferase TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. TUNEL positive myocytes and some nonmyocytes appeared in the subepicardium at 6 hours after ISO administration. The localization of these cells was shifted to the subendocardium within 24 hours, and the TUNEL positive cells were seen throughout the myocardium on the 5th day after ISO treatment. Necrotic myocyte death occurred on the 3rd day of ISO administration in the subendocardium, and initial pericellular fibrosis was followed and increased thereafter, with replacement fibrosis accompanied by further necrotic myocyte cell death.
CONCLUSIONS
Our data showed that ISO treatment induced apoptotic myocyte death and superimposed necrotic myocyte death with subsequent fibrosis. The observed cardiac myocyte death may reflect myocardial dysfunction.

Altered Expression of Tissue Inhibitor of Matrix Metalloproteinase-2 in Complicated Mice Heart Secondary to Experimentally Induced Viral Myocarditis.: Sung Sook Kim, Dae Woon Eom, Yeong Ju Woo, Jae Hee Suh, Jooryung Huh, Young Me Hong, Inpyo Choi; Korean J Pathol. 2001;35(3):196-200.

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Abstract PDF: BACKGROUND
The pathogenesis of transition from viral myocarditis to dilated cardiomyopathy is elusive, although the incidence of dilated cardiomyopathy in human is increasing.
METHODS
To clarify the role of the tissue inhibitor of matrix metaloproteinase-2 (TIMP-2) in this event, we performed immunohistochemistry, immunoblotting and immunoassay of matrix metalloproteinase-9 (MMP-9) and TIMP-2 in the serum and heart tissue of mice, which were inoculated with 4000 plaque-forming units of coxsackie B virus.
RESULTS
The MMP-9 was expressed in damaged cardiomyocytes, and the TIMP-2 was expressed in mainly interstitial connective tissue between cardiac muscle bundles by immunohistochemistry. The level of serum MMP-9 was higher in the complicated than non-complicated group (p<0.001), but the level of TIMP-2 was much lower in complicated than non-complicated group (p<0.05). These findings were similar to the results of immunohistochemistry and immunoblotting in tissues.
CONCLUSIONS
These results suggest that an imbalance in the level of MMP-9 and its inhibitor might activate cardiac complication in viral myocarditis.

The Increased Expression and Diagnostic Usefulness of CD56 Antigen in Paraffin Embedded Plasma Cell Neoplasm.: Seok Hyung Kim, Chan Sik Park, Eun Young Choi, Hyun Wook Kang, Seong Hoe Park, Doo Hyun Chung; Korean J Pathol. 2001;35(3):201-205.

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Abstract PDF: BACKGROUND
The natural killer cell antigen CD56 (NCAM) is a member of the immunoglobulin superfamily and is expressed on neurons, astrocytes, and Schwann cells. Recently, it has been reported that CD56 expression is detected on plasma cells of multiple myeloma by flow cytometry.
METHOD
In this study, to test the diagnostic usefulness of the anti-CD56 antibody for plasma cell neoplasm on paraffin-embedded materials, we performed immunohistochemical staining of samples from 19 patients with plasma cell neoplasms. These cases included 14 cases of multiple myeloma, 3 cases of solitary plasmacytoma of the bone, and two cases of extramedullary plasmacytoma.
RESULTS
The neoplastic plasma cells from 68 % of the patients with plasma cell neoplasms expressed CD56 highly. CD56 was expressed in all three cases of solitary plasmacytoma of the bone and one of two extramedullary plasmacytoma, and nine out of 14 multiple myeloma cases. In contrast, reactive plasma cells from the 18 patients with miscellaneous lesions were completely negative for CD56.
CONCLUSIONS
CD56 is aberrantly expressed on the neoplastic plasma cells, and it may be used as a useful marker for the diagnosis of plasma cell neoplasms in paraffin-embedded tissues.

Image Analysis of Glomerular Changes in Patients with Post-transplant IgA Nephropathy.: Kye Won Kwon, Hyeon Joo Jeong; Korean J Pathol. 2001;35(3):206-211.

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Abstract PDF: BACKGROUND
IgA nephropathy after renal transplantation (post-transplant IgAN) may recapitulate the IgAN of native kidneys, however, little has been reported about the histologic characteristics. The aim of this study is to apply glomerular morphometry using an image analyser to examine the histologic characteristics of post-transplant IgAN.
METHODS
The outer margin of the glomerulus (Bowman's area, BA) and glomerular tuft area (GA) were traced manually. The measured area were automatically calculated by KS300 image analysis system (Kontron, Munchen, Germany). The mesangial area (MA) was calculated with a summing each manually traced mesangial area. The total number of glomerular (GC) and mesangial cells (MC) were counted. Eight cases of renal section obtained by nephrectomy due to renal cell carcinoma (normal control: N-CTRL) and nineteen cases of renal section obtained from post-transplantation patients without IgAN (transplantation control: Tx-CTRL) served as controls.
RESULTS
A total of 35 biopsies were finally selected for measurement. BA and GA of post-transplant IgAN were 1.6 and 1.4 times larger than the N-CTRL, respectively, and were not significantly different from Tx-CTRL. MA was 1.4 times significantly larger than that of the Tx-CTRL. As compared to that of the N-CTRL, it was 1.2 times larger, but this difference was not statistically significant. The GC and MC of post-transplant IgAN and the Tx-CTRL were significantly lower than the N-CTRL. There were no significant correlations between glomerular hypertrophy and duration after renal transplantation, mesangial changes, segmental sclerosis, or degree of renal cortical interstitial fibrosis in post-transplant IgAN.
CONCLUSIONS
Prominent glomerular hypertrophy and mesangial expansion suggest a hyperfiltration injury in post-transplant IgAN and a possible way to glomerulosclerosis.

Immunohistochemical Expression of p53, p21, and mdm2 Proteins in Human Papillomavirus Positive and Negative Invasive Uterine Cervical Carcinomas.: In Seo Park, Hye Seung Han, Tae Sook Kim, Jee Young Han, Joon Mee Kim, Young Chae Chu, Tae Sook Hwang; Korean J Pathol. 2001;35(3):212-219.

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Abstract PDF: BACKGROUND
In the uterine cervical carcinoma, the inactivation of p53 protein by human papillomavirus(HPV) E6 protein has been reported to play a greater role in carcinogenesis than the mutation of the p53 gene. Therefore, the mutation of the p53 gene is rare. p21 and mdm2 proteins are induced by wild-type p53 protein and are involved in the cell cycle regulatory mechanism.
METHODS
Immunohistochemical staining for p53, p21 and mdm2 proteins was performed in 26 HPV-positive and 13 HPV-negative invasive cervical carcinomas together with 5 non-neoplastic cervical tissues.
RESULTS
The frequencies of the expression of p53, p21 and mdm2 proteins were 82.1%, 84.6% and 66.7%, respectively. The expression of p53 protein was less frequently demonstrated in HPV-positive cases than HPV-negative cases, which was statistically a negative correlation(p=0.018). The expression of p53 and p21 proteins was statistically significant(p=0.000).
CONCLUSIONS
p53, p21 and mdm2 proteins were highly expressed in both HPV-positive and HPV-negative cervical carcinomas. Significantly higher expression of p53 protain in HPV-negative cases necessitate a further study for investigating the role of p53 protein accumulation in carcinogenesis of HPV-negative cervical carcinomas. The relationship between the expression of p53 protein and p21/mdm2 proteins may indicate that p21 and mdm2 proteins also have a role in carcinogenesis, where p53 protein plays a fundamental role.

Expression of p27kip1 and Cyclin D1 in Serous Epithelial Ovarian Tumors.: Sun Young Kwon, Eun Sook Chang, Kun Young Kwon, Kwan Kyu Park, Soo Kyung Kim; Korean J Pathol. 2001;35(3):220-225.

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Abstract PDF: BACKGROUND
p27kip1 is a member of the Cip/Kip family of the cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Decreased expression of p27kip1 is associated with high histologic grade and poor prognosis in a variety of human tumors.
METHODS
Sixty-six cases of serous epithelial ovarian tumors were investigated by immunohistochemical staining for p27kip1, cyclin D1, and Ki-67. Clinicopathologic parameters (WHO classification, histologic grade and FIGO stage) were compared with the incidence of p27kip1, cyclin D1 and Ki-67 protein expression in ovarian serous tumors.
RESULTS
Reduced expression of p27kip1 was found more freguently in serous cystadenocarcinoma than in serous cystadenoma and borderline malignancy (p<0.05). The decreased expression of p27kip1 was correlated with a high histologic grade and an advanced FIGO stage. Overexpression of cyclin D1 is associated with borderline malignancy and grade I serous cystadenocarcinoma. An inverse relationship was observed between the p27kip1 protein and the Ki-67 labeling index within serous cystadenocarcinoma, but it was not significant.
CONCLUSIONS
Reduced expression of p27kip1 protein plays an important role in the biologically aggressive behavior of serous epithelial ovarian tumors and might represent a useful prognostic marker for predicting the recurrence in primary ovarian tumors.

Expression of Cytokeratin 1, 10 and 14 in Fetal Skin.: Kye Yong Song, Sun Lee, Dong Hye Suh, Mi Kyung Kim, Hye Jung Min, Je G Chi; Korean J Pathol. 2001;35(3):226-231.

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Abstract PDF: BACKGROUND
During the fetal stage, the epidermis and adnexal epithelium might express different types of cytokeratin (CK) by developmental stages. The objective of this study is to observe the expressions of CK1, CK10 and CK14 in the skin of human fetuses.
METHODS
Immunohistochemical stains were applied to the skin of 42 fetuses ranging from 10 to 36 gestation weeks. Three different portions of the body (i.e., scalp, chest and sole) were sampled. Immunohistochemical staining with monoclonal antibodies against CK1, 10, 14 were done.
RESULTS
We found that CK14 was expressed in the basal layer of the epidermis and adnexae of fetuses beween 10 to 36 gestation weeks. However, stronger expression in the middle than the basal layer was noted in the soles of 15-week fetuses followed by exclusive basal expression. The sebaceous gland, the outer root sheath of the hair follicle and the eccrine duct epithelium also showed CK14 expressions, while CK14 was negative in hair germ and acini. Both CK1 and CK10 were expressed in the epidermis of fetuses ranging between 10 to 36 gestation weeks at the suprabasal layer of the scalp, chest and sole; while they were negative in the basal layer and skin adnexae including sebaceous, hair and eccrine gland.
CONCLUSIONS
Expression of cytokeratins in the fetal skin were noted at 10 weeks throughout the entire gestation period and were similar in the three different sites, except in the early stage of the sole. The main expression sites of K14 were the basal layer of the epidermis, the eccrine ducts and the outer root sheath cells of hair, suggesting the same origin, while those of K1 and K10 were in the suprabasal layer of epidermis.

ras Gene Mutations in Malignant Fibrous Histiocytoma.: Jinyoung Yoo, Ah Won Lee, Seok Jin Kang, Byung Kee Kim; Korean J Pathol. 2001;35(3):232-237.

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Abstract PDF: BACKGROUND
ras gene mutations have been described in various human malignancies, suggesting that their activation may play a role in oncogenesis. However, there are few reports concerning ras gene alterations in malignant fibrous histiocytomas. We therefore designed a study to determine the prevalence and type of mutations in the first exons of H-ras and K-ras genes in these tumors.
METHODS
Twenty-seven malignant fibrous histiocytomas were investigated by direct sequencing analysis with the automated DNA sequencing of polymerase chain reaction-amplified ras sequences.
RESULTS
Twenty-four mutations were found in 18 (67%) of the tumors: GGC to GAC transition mutations at codon 13 of K-ras (coding for aspartic acid instead of glycine) in 18 of the samples and GGC to GTC transversions at codon 12 of H-ras (coding for valine instead of glycine) in six of the lesions.
CONCLUSIONS
Our data suggest an involvement of the ras gene mutation in conjunction with other yet unknown events in the tumorigenesis and/or progression of malignant fibrous histiocytomas. The K-ras gene activation predominated in these tumors by a mutation at codon 13. It is noteworthy that H-ras mutations were detected only in association with the lesions containing K-ras mutated genes, the significance of which remains to be determined.

Expression of Cyclin D1, CDK4, p16 and Rb Proteins in Human Soft Tissue Sarcomas.: Jinyoung Yoo, Ah Won Lee, Seok Jin Kang, Byung Kee Kim; Korean J Pathol. 2001;35(3):238-244.

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Abstract PDF: BACKGROUND
Altered cell cycle regulation may underlie the development and/or progression of human malignancies. The purpose of this study is to determine if the oncogenesis of soft tissue sarcomas could be better explained by examining the components involved in G1 phase progression.
METHODS
Sixty-seven soft tissue sarcomas were studied for the immunohistochemical expression of cdk4, cyclin D1, retinoblastoma (Rb) and p16 proteins. For Rb and p16, samples showing either negative or heterogeneous (<80% of tumor cells) staining were considered to be altered.
RESULTS
The cdk4 protein was observed in 64 cases (95.5%). Cyclin D1 was expressed in 14 cases (20.9%). The Rb expression was altered in 48 (71.6%). Sixty-three (94%) sarcomas demonstrated altered p16 expressions. All of the samples displayed altered expressions of either Rb or p16. A high percentage of the tumors with altered Rb were observed in relapsed patients (p<0.05).
CONCLUSIONS
Disturbance in the cell cycle regulatory system involving the Rb/p16/cdk4/cyclin D1 pathway appears to be relatively frequent in soft tissue sarcomas and may play an important role in the tumorigenesis of these tumors. It is noteworthy that the reduced Rb expression correlates with tumor relapse, suggesting its prognostic significance.

Case Reports

Nevus Cell Inclusions in the Lymph Node: A Report of Two Cases.: Ji Sun Song, Tae Woong Noh, Yoon Mee Kim, Sang Ho Cho, Kwang Gil Lee; Korean J Pathol. 2001;35(3):245-247.

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Abstract PDF: Nevus cell inclusion in the lymph node is an uncommon histologic finding and usually is an incidental finding in the capsule, fibrous trabeculae, perinodal adipose tissue, and parenchyma of the axillary, inguinal, or cervical lymph nodes which are removed as part of cancer diagnostic or therapeutic procedures. The aggregated pigmented nevus cells in the lymph node resemble the cells of the cutaneous nevi. It is important to differentiate them from metastatic carcinoma or malignant melanoma. The characteristic features of nevus cell inclusions are presence of nevus cells within the capsule and supporting stroma, without presence in the marginal sinus of the lymph node, and the absence of cytological atypia or mitosis of nevus cells. We report two cases of nevus cell inclusions, in the axillary lymph nodes in a patient with breast carcinoma and in an enlarged inguinal lymph node in a patient without a malignant tumor.

Nasal Inverted Papilloma Associated With Squamous Cell Carcinoma: A Report of Two Cases.: Mi Jin Gu, Dong Sug Kim, Young Kyung Bae, Yong Dae Kim; Korean J Pathol. 2001;35(3):248-281.

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Abstract PDF: Nasal inverted papilloma (IP) is a benign neoplasm that may be associated with squamous cell carcinoma (SCC). Several studies have suggested that human papilloma virus 16/18 (HPV 16/18) and p53 are closely related to the pathogenesis of IP with transformation to squamous cell carcinoma (IP-SCC). This study was conducted to investigate the role of HPV 16/18 and p53 in the pathogenesis of IP-SCC using immunohistochemistry. We studied two cases of IP-SCC and 10 cases of IP. None of the IP cases presented positivity for HPV 16/18 or p53 protein. Two cases of IP-SCC showed negative reactions for HPV 16/18. The SCC portion of the IP-SCC showed strong positivity for p53, while the IP portion of the IP-SCC was negative for p53. MIB-1 labeling index (LI) was estimated in the IP cases and the IP-SCC as well. In terms of MIB-1 LI, there was no statistical significance between IP and IP-SCC, and between the IP portion and the SCC portion in the cases of IP-SCC. In conclusion, we believe that alteration of the p53 protein is related to IP with malignant transformation, but further studies are required to investigate the correlation of HPV 16/18 and p53 in the pathogenesis of IP with malignant transformation, and the significance of the MIB-1 LI and p53 as biomarkers in IP.

Malignant Gastrointestinal Stromal Tumor of the Esophagus: A Case Report.: Hae Joung Sul, Kyeong Hee Kim, Dae Young Kang; Korean J Pathol. 2001;35(3):252-255.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) predominate in the stomach and small intestine but have rarely been documented in the esophagus. We report a rare case of GIST of the esophagus in a 47-year-old woman. Histologically, the tumors showed a combination of solid, myxoid, and perivascular collar-like patterns, with spindle and epithelioid cells. The tumor cells were positive for CD117, CD34, and S-100 protein and negative for desmin and -smooth muscle actin.

Myxoglobulosis of the Appendix: A Case Report.: Jong Yup Bae, Jong Woo Kim; Korean J Pathol. 2001;35(3):256-258.

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Abstract PDF: Myxoglobulosis of the appendix is a rare and peculiar form of appendiceal mucocele. It is characterized by pearl or fish egg-like mucin globules in the lumen. We report a case of myxoglobulosis of the appendix in a 31-year-old man. Myxoglobules are composed of eosinophilic necrotic cell debris and mucin in the central nidus and lamellar structures alternating with necrotic cell debris and mucin in the peripheral zone. A stirring effect produced by vigorous appendiceal peristalsis may contribute to its lamellar growth.

Cellular Angiofibroma of the Vulva: A Report of Three Cases.: Hye Jeong Choi, Sung Nam Kim, Kyu Rae Kim; Korean J Pathol. 2001;35(3):259-262.

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Abstract PDF: Cellular angiofibroma is a recently described, distinctive soft tissue tumor of the vulvovaginal region which is characterized by small, well-circumscribed tumors with fibroblastic differentiation. We report three cases of cellular angiofibroma of the vulva in middle-aged women. All three patients presented with painless swelling in the labium majora. The age of the three patients ranged from 43 to 56 years old (mean: 48 years old) and the size of the tumor ranged from 2 to 5 cm. The microscopic appearance was characterized by a cellular, well-circumscribed mass composed of uniform, bland, spindle stromal cells, numerous thick-walled, hyalinized vessels, and a scarce component of mature adipocytes. Immunohistochemical stains of the tumor cells show positivity for vimentin but negativity for smooth muscle actin, S-100 protein, desmin, factor VIII-related antigen and epithelial membrane antigen. The tumor should be differentiated from aggressive angiomyxoma and angiomyofibroblastoma because of its different clinicopathologic features, cells of origin and immunohistochemical findings.

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