Journal of Pathology and Translational Medicine

Volume 39(5); October 2005

Original Articles

Ovarian Borderline Epithelial Tumors.: Geunghwan Ahn; Korean J Pathol. 2005;39(5):291-300.

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Abstract PDF: Ovarian borderline epithelial tumors are abnormal proliferative epithelial lesions without obvious invasion of the stroma of the ovary, a finding distinguishing between borderline tumors and carcinoma. There have been controversies regarding the terminology and diagnostic feature of the tumors, even though these tumors have been accepted as a distinct entity in WHO classification of ovarian epithelial tumors. This review is limited to serous and mucinous borderline tumors which are the most common and about which many clinicopathological studies have been undertaken. It has been agreed that "micropapillary carcinoma" espoused by a group of pathologists is a micropapillary variant of serous borderline tumor in the borderline ovarian tumor workshop. Diagnostic criteria of invasive implants needs further study but invasion of underlying normal tissue was reported to be correlated well with prognosis. Other issues such as diagnostic criteria of microinvasion and multiplicity of serous borderline tumors have been presented. The sole diagnostic criteria agreed upon for the diagnosis of intraepithelial carcinoma in the mucinous borderline tumor was the presence of severe cytological atypia. It was also agreed that the ovarian tumors associated with pseudomyxoma peritonei are almost invariably from gastrointestinal tract, usually appendix. Stratification and complex intracystic growth without severe cytological atypia are considered to be characteristics of mucinous borderline tumors. Diagnostic criteria of microinvasion and two types of invasion, expansile and infiltrative invasion, have also been discussed.

Expressions of E2F4 and E2F2 Transcription Factors in Breast Carcinoma.: Eun Young Kim, Hyun Jin Jo, Mi Ja Lee; Korean J Pathol. 2005;39(5):301-306.

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Abstract PDF: BACKGROUND
The E2F family (E2F1 to E2F6) of transcription factors plays a key role in cell cycle progression. Some act as oncogenes and others act as tumor suppressor genes (TSG) in a tissue-specific manner. E2F4 may function as a TSG. However, the role of E2F4 in breast carcinogenesis remains controversial. Also the clinical impact of E2F2 expression on breast cancer remains unknown.
METHODS
Expressions of E2F4 and E2F2 were assessed immunohistochemically in 113 breast carcinomas and were compared with clinicopathological variables, expressions of G1/S checkpoint proteins (p16, cyclin D1 and Rb), and DNA ploidy to identify their possible role and to assess their prognostic value in breast cancer.
RESULTS
Expressions of E2F4 and E2F2 were detected in 48 cases (42.5%) and 66 cases (58.4%), respectively. Expressions of E2F4 and E2F2 were significantly correlated with large tumor size (p<0.001) and lymph node metastasis (p<0.001). There was no correlation between expressions of E2F4 or E2F2 and any other variables, including age, histologic grade, DNA ploidy and expressions of p16, cyclin D1 and Rb.
CONCLUSIONS
These results suggest that expressions of E2F4 and E2F2 are associated with growth and spread of breast cancer and indicate poor prognosis.

Expression of Hypoxia Inducible Factor-1alpha in Invasive Squamous Cell Carcinoma of Uterine Cervix Treated by Radiotherapy.: Kyung Ja Lee, Min Sun Cho, Seung Cheol Kim, Hae Sung Moon, Hyesook Park, Shi Nae Lee, Sun Hee Sung, Ki Nam Shim, Kyung Eun Lee, Sung Ae Jung, Kwon Yoo, Hae Young Park, Soo Yeun Park, Eun Sun Yoo, Hyun Suk Suh; Korean J Pathol. 2005;39(5):307-312.

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Abstract PDF: BACKGROUND
Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia, and this is associated with reduced radiosensitivity. Furthermore, HIF-1alpha can increase a tumor's aggressiveness by promoting neoangiogenesis, cell proliferation and survival, and invasion.
METHODS
The expression of HIF-1alpha was was investigated by performing immunohistochemistry on the cervical tissue specimens obtained from 57 patients who had received radiotherapy combined with or without chemotherapy for stages I-III cervical squamous cell carcinoma. The staining results were compared with anemia, the stage, the radiotherapy response and patient survival by univariate and multivariate analysis.
RESULTS
In 57 patients, the expression of HIF-1alpha was seen in the tissue specimens of 46 patients (81.7%). Among them, 25 (54.3%), 14 (30.4%), and 7 (15.2%) of the patients' tissue specimens showed weak, moderate and strong expressions, respectively. Six patients had a partial response after radiotherapy. Twelve patients (21.1%) died of cervical cancer. The increased expression of HIF-1alpha was significantly associated (p<0.05) with the disease stage and anemia. There were significant positive correlations between the increased expression of HIF-1alpha and the poor response after radiotherapy and the patients' survival.
CONCLUSIONS
The present result suggests that the overexpression of HIF-1alpha in the uterine cervix could be used as a prognostic indicator for the patients treated with radiotherapy.

Mutational and Loss of Heterozygosity Analysis of the p53 and PTEN Tumor Suppressor Genes in Breast Carcinoma.: Kwang Sun Suh, Young Ho Lee, Sun Young Na, Moon Il Park, Hun Soo Kim, Saeng Keum Lee; Korean J Pathol. 2005;39(5):313-319.

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Abstract PDF: BACKGROUND
Although the genetic determinants of most sporadic breast cancers remain unknown, the understanding of the molecular and genetic events that contribute to breast carcinogenesis has been significantly advanced. We investigated the clinicopathologic significance of allelic imbalance or mutation of both p53 and PTEN tumor suppressor genes in sporadic breast carcinomas.
METHODS
Genomic DNA from 62 breast carcinoma cases was extracted from paraffin blocks, and PCR was performed to determine loss of heterozygosity (LOH) for DNA markers around the p53 and PTEN genes and to amplify exons 5, 6, 7, and 8 of p53 and all 9 coding axons of PTEN.
RESULTS
Somatic p53 mutations were detected in 6 (9.7%) of the 62 cases. LOH for DNA markers surrounding p53 was observed in 18 (29.0%) of the 62 cases. LOH for DNA markers surrounding PTEN was detected in 29 (46.8%) of the 62 cases. Only one case (1.6%) showed somatic PTEN mutations. Tumors with LOH on 17p or p53 mutation were large in size and negative for ER, had a high Ki-67 index, and exhibited p53 immunoreactivity (p<0.05). Tumors with LOH on 10q23 were associated with c-erbB-2 positivity (p=0.018).
CONCLUSIONS
Our results indicate that LOH at 17p and/or p53 mutation is significantly associated with the aggressive pathologic parameters of breast cancer.

Survivin and Fas Ligand Expressions Are Correlated with Angiolymphatic Tumor Spread in Medullary Thyroid Carcinoma.: Min Kyung Kim, Jin Hee Sohn, Mee Joo, Hanseung Kim, Sung Hye Park, Seong Hoe Park, Eo Jin Kim, Seoung Wan Chae; Korean J Pathol. 2005;39(5):320-325.

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Abstract PDF: BACKGROUND
Medullary thyroid carcinoma (MTC) that originates from C cells comprises about 10% of all the malignant thyroid tumors. Activating mutations of the RET proto-oncogene have been found to be involved in the anti-apoptotic pathway of MTC that harbors the RET mutation. We investigated the correlation between the clinicopathologic parameters and the expressions of survivin, a novel anti-apoptotic molecule, and the other apoptosis-related proteins, and the known prognostic markers.
METHODS
Immunohistochemical staining was performed using antibodies for survivin, Fas, Fas ligand (FasL), bcl-2, calcitonin, CEA and cyclin A in 19 case of MTC; 10 sporadic MTCs, eight multiple endocrine neoplasia (MEN) type 2A MTCs and one familial MTC (FMTC).
RESULTS
Survivin protein expression was found in five cases (26%) and this was correlated with the presence of angiolymphatic tumor emboli (p=0.019). FasL was expressed in 14 cases (74%) and it had correlation with the presence of lymph node metastases (p=0.029). The cyclin A-labeling indices were correlated with local invasiveness (p=0.001).
CONCLUSIONS
Survivin and FasL might be involved in the lymphatic tumor spread of MTC.

Immunohistochemical Analysis of Insular Carcinoma of the Thyroid Gland.: Hye Sook Min, Jin Ho Paik, Kyoung Bun Lee, Seong Hoe Park, Doo Hyun Chung; Korean J Pathol. 2005;39(5):326-331.

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Abstract PDF: BACKGROUND
Insular thyroid carcinoma (ITC) is a relatively infrequent thyroid carcinoma that has distinctive histologic features. ITC shows an aggressive clinical course and the predominant presence of an insular component, which has been reported to be an independent factor of a poor prognosis. We retrospectively examined clinical details of the nine ITC patients, which represented 9 years of experience with ITC, and investigated the expressions of variable neuroendocrine and other immunohistochemical markers associated with well-differentiated thyroid carcinomas.
METHODS
We adopted an immunohistochemical approach and studied the expressions of synaptophysin, chromogranin A, CD56, NSE, S-100, RET, PPARgamma, calcitonin, galectin-3, and thyroglobulin in formalin-fixed, paraffin embedded tissue array slides of the 9 ITC patients, and investigated clinical features. Seven cases of follicular carcinoma and 4 cases of medullary carcinoma were also included as controls.
RESULTS
ITCs were positive for synaptophysin (44%, 4/9), CD56 (11%, 1/9), NSE (89%, 8/9), S100 (67%, 6/9), calcitonin (22%, 2/9), galectin-3 (78%, 7/9), and thyroglobulin (100%, 9/9), but completely negative for chromogranin A, RET, and PPARgamma.
CONCLUSION
ITCs express neuroendocrine markers in variable proportions and appear not to be associated with the oncoproteins of conventional thyroid carcinomas. Notably, its differential diagnosis from medullary carcinoma is required in cases showing focal calcitonin positivity.

Altered Expression of DNA Topoisomerase IIalpha, Ki-67, p53 and p27 in Non-Hodgkin's Lymphoma.: Kyeong Min Lee, Mee Young Sol, Hyun Jeong Kang, Dong Hoon Shin, Kyung Un Choi, Hwal Woong Kim, Jee Yeon Kim, Do Youn Park, Chang Hun Lee; Korean J Pathol. 2005;39(5):332-337.

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Abstract PDF: BACKGROUND
Topoisomerase II (TOPO II) is an enzyme that separates intertwined chromosomes during DNA synthesis by transiently breaking and joining DNA strands. The level of TOP II is one of the determinants of cellular sensitivity to anti-tumor drugs in non-Hodgkin's lymphoma patients. The alpha form of TOPO II has been recently used as a marker of cellular proliferation. High levels of TOPO IIalpha are expressed in aggressive and proliferative tumors.
METHODS
This study was designed to evaluate the relationship between TOPO IIalpha expression and clinicopathological parameters including age, gender, the serum LDH level, the serum beta2-microglobulin level and stage, or expressions, of Ki-67, p53 and p27, in non-Hodgkin's lymphoma. We analyzed forty-one biopsied tissue specimens from patients with non-Hodgkin's lymphoma.
RESULTS
The expression of TOPO IIalpha increased with the clinical stage and it was correlated with Ki-67 and p53 expressions. However, TOPO IIalpha expression did not have any significant correlation with age, gender, the serum LDH level, the serum 2-microglobulin level and the p27 expression.
CONCLUSIONS
TOPO IIalpha expression is a useful marker of cellular proliferation and it may serve as a prognostic factor of a tumor's progression and aggressiveness in non-Hodgkin's lymphomas.

The Loss of Expression of Caveolin-1 in Gastrointestinal Stromal Tumors.: Eo Jin Kim, Jin Hee Sohn, Min Kyung Kim, Seoung Wan Chae, Hye Seung Lee, Eun Yoon Cho, Woo Ho Kim; Korean J Pathol. 2005;39(5):338-344.

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Abstract PDF: BACKGROUND
The down-regulation of caveolin-1, a putative tumor suppressor gene, has been demonstrated in several types of sarcomas. However, it's not known whether or not the gastrointestinal stromal tumors (GISTs) express caveolin-1. We carried out this study to investigate the caveolin-1 expression in GISTs and to determine the correlation between the clinicopathologic profiles of GISTs and the expression of caveolin-1.
METHODS
One hundred eight cases of formalin-fixed and paraffin-embedded tissues of GISTs were immunohistochemically evaluated for the expression of caveolin-1 by using the tissue-array method. Survival data of 98 cases of primary GISTs was analysed according to the expression status of caveolin-1.
RESULTS
Ninety three cases (86.1%) of 108 GISTs did not express caveolin-1 protein. There was no correlation between the caveolin-1 expression status and any of the clinicopathologic variables, including mitosis (p=0.948) and tumor grade (p=0.334). The expression of caveolin-1 was not correlated with other immunohistochemical marker proteins including, c-kit (p=0.373), CD34 (p=0.437) and SMA (p=0.831). On the univariate analysis, the caveolin-1 expression status (p=0.635) was not a significant predictor of the disease-free survival for GIST patients.
CONCLUSIONS
The results of this study suggest that caveolin-1 might act as a tumor suppressor gene in the GIST oncogenesis, but it has no function as a prognostic marker for disease free survival.

Case Reports

Xanthomatous Pseudotumor of the Breast: A Brief Case Report.: Lee So Maeng, Se Jeong Oh, Kyoung Mee Kim, Anhi Lee, Chang Suk Kang; Korean J Pathol. 2005;39(5):345-347.

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Abstract PDF: Inflammatory (xanthomatous) pseudotumors of the breast are very rare and this case is the first reported case in Korea. A healthy, pregnant 29-year-old woman presented with a right breast mass. Ultrasonography of the breast revealed a 1.8 x 1.9 x 1.1 cm, sized lobulated, partially spiculated mass in the upper and outer quadrant of the breast. Macroscopically, the mass was well circumscribed, bright yellow, and lobulated. Microscopically, the tumor was composed of foamy histiocytes with multifocal neutrophilic infiltration, accompanying chronic inflammatory cellul infiltration, fibrosis and ductal-lobular atrophy.

Epidermoid Cyst in the Kidney with Nephrolithiasis: A Case Report.: Changyoung Yoo, Yeong Jin Choi, Kyoyoung Lee, Sang In Shim, Chang Suk Kang; Korean J Pathol. 2005;39(5):348-350.

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Abstract PDF: Epidermoid cysts in the kidney have rarely been reported, and in most cases its pathogenesis has not been well understood. We report a case of an epidermoid cyst in a kidney with nephrolithiasis in a 61-year-old man. A pyelonephrolithotomy was performed on the patient four years ago to treat nephrolithiasis of the left kidney. During the follow-up, a newly developed mass was discovered three years ago and the mass has recently increased in size. A unilateral nephrectomy was performed under the clinical impression of renal cell carcinoma. Gross examination revealed a well encapsulated cystic mass measuring 3.0 x 2.0 x 2.0 cm and containing lumps of soft whitish material, in the upper pole of the left kidney. This location was the same as that of previous nephrolithiasis. Microscopic examination revealed typical findings of an epidermoid cyst. We suspect that the chronic irritation induced by renal stones may be associated with the development of the epidermoid cyst in this case.

Benign Histiocytoma of the Lung: A Case Report.: Myoung Ja Chung, Min Ho Kim, Hyun Jin Son; Korean J Pathol. 2005;39(5):351-355.

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Abstract PDF: Histiocytomas have rarely been reported in the lungs. We report an unusual benign pulmonary histiocytoma in a 45-year-old man and discuss the differential diagnosis. Chest CT showed a well-defined solitary pulmonary nodule of approximately 3 cm in size in the posterobasal segment of the right lower lobe. Posterolateral thoracotomy and wedge resection was performed. Gross examination revealed a mass, measuring 2.2 x 2.1 cm that had a circumscribed margin within the lung parenchyma. Microscopically, the tumor was entirely composed of large polygonal to round cells with a few chronic inflammatory cells. These tumor cells contained abundant cytoplasm which was either granular, eosinophilic or foamy. Immunohistochemically, these cells were diffusely positive for CD68 and focally positive for 1-antitrypsin, but negative for cytokeratin, vimentin, and smooth muscle actin.

Histiocytic Sarcoma of the Spleen: A Case Report and Review of the Literature.: Jin Ho Paik, Yoon Kyung Jeon, Sung Shin Park, Hye Sook Min, Young A Kim, Ji Eun Kim, Chul Woo Kim; Korean J Pathol. 2005;39(5):356-359.

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Abstract PDF: True histiocytic sarcoma is an extremely rare tumor. Its clinicopathological features are not clearly understood. Here, we report the first Korean case of primary splenic histiocytic sarcoma. A 64-year-old female having refractory thrombocytopenia, anemia and splenic mass was admitted to the hospital, and received splenectomy. Grossly, spleen was enlarged up to 18 x 13 x 8 cm and occupied with multinodular masses. Microscopically, the masses were composed of atyical large cells with abudant cytoplasm and vesicular nuclei with prominent hemophagocytosis. The tumor cells were CD68 (+), S-100 protein (-), CD21 (-), CD1a (-). After splenectomy, thrombocytopenia and anemia were corrected. However two months later the symptoms recurred, and the patient died 15 months after splenectomy. This case shared the common clinicopathologic features with the several previously reported cases in other countries, represented by splenic mass formation and prominent hemophagocytosis associated with thrombocytopenia and anemia, often leading to poor outcome.

Sarcomatoid Carcinoma of the Distal Common Bile Duct: A Case Report.: Ki Seok Jang, Si Hyong Jang, Young Ha Oh, Ho Soon Choi, Kyeong Geun Lee, Dongho Choi, Seung Sam Paik; Korean J Pathol. 2005;39(5):360-363.

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Abstract PDF: Sarcomatoid carcinoma of the common bile duct (CBD) is an extremely rare malignant neoplasm, which is characterized by the presence of carcinomatous and sarcomatous components. We report a case of sarcomatoid carcinoma arising in the distal CBD. The patient was a 68- year-old woman who presented with abdominal pain. The computed tomography and endoscopic ultrasonography revealed a polypoid mass in the distal CBD. The resected specimen showed a polypoid mass with a narrow stalk in the distal CBD which was confined to the mucosa. The cut surface revealed a gray-whitish solid mass with focal hemorrhage and necrosis. Microscopically, the tumor was composed of carcinomatous and sarcomatous components without any heterologous elements. The sarcomatous area predominently consisted of pleomorphic spindle cells. The carcinomatous component was an adenocarcinoma. On immunohistochemistry, cytokeratin was coexpressed in the carcinomatous and sarcomatous components but vimentin was expressed exclusively in the sarcomatous component. The patient has been doing well for one year postoperatively.

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