Journal of Pathology and Translational Medicine

Volume 39(1); February 2005

Original Articles

PTEN and p53 Mutations in Endometrial Carcinomas.: Jae Sung Choi, Kwang Sun Suh, Heung Tae Noh, Yun Ee Rhee, Sun Young Na, Hye Kyung Lee; Korean J Pathol. 2005;39(1):1-8.

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Abstract PDF: BACKGROUND
Endometrial carcinomas are pathogenetically classified into two major types; endometrioid carcinoma (EC) and serous carcinoma (SC). The most frequently altered gene in EC is the PTEN tumor suppressor gene (TSG). SC is usually associated with mutations in the p53 TSG.
METHODS
To further determine the role of PTEN and p53 mutation in endometrial carcinogenesis, the analysis of 33 endometrial carcinomas, including 28 ECs and 5 SCs, for loss of heterozygosity (LOH) on 10q23 and for mutation in all 9 coding exons of PTEN and the 5-8 exons of p53, using SSCP-PCR methods was carried out.
RESULTS
LOH was detected in at least one marker in 12 (54.5%) of 22 ECs, but in only one (20.0%) of 5 SCs. Somatic PTEN mutations were detected in 10 (35.7%) of 28 ECs. PTEN was altered in 67.9% of ECs and in 20.0% of SCs, including those with 10q23 LOH. No PTEN mutations were found among the SCs. Somatic p53 mutations were detected in 2 (7.1%) of 28 ECs and 3 (60.0%) of 5 SCs.
CONCLUSIONS
PTEN gene alterations contribute to the pathogenesis of an endometrioid subtype of endometrial carcinoma, but not to the serous type. In contrast, p53 plays an important role in the pathogenesis of SCs.

Microsatellite Instability and Mismatch Repair Protein (hMLH1, hMSH2) Expression in Intrahepatic Cholangiocarcinoma.: Yun Kyung Kang, Woo Ho Kim; Korean J Pathol. 2005;39(1):9-14.

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Abstract PDF: BACKGROUND
To clarify the role of the mismatch repair (MMR) system in the carcinogenesis of intrahepatic cholangiocarcinoma (ICC), we investigated the microsatellite instability (MSI) status and MMR protein expression in ICC.
METHODS
Thirty-six cases of ICCs were examined by microsatellite analysis for 55 markers that encompassed all of the chromosomal arms and BAT26. An immunohistochemical study for hMLH1 and hMSH2 was also performed.
RESULTS
Widespread MSI (MSI-H) accompanied with a loss of hMLH1 expression was found in one case (2.8%). This MSI-H case was an adenosquamous carcinoma showing intraductal tubulopapillary adenocarcinoma and invasive adenosquamous carcinoma component. Loss of hMLH1 was noted in both components while the frequency and shifted band patterns of MSI were not identical between the components. Another 10 ICCs (27.8%) revealed low level MSI with preserved MMR gene expression.
CONCLUSIONS
Our data suggested that a genetic defect in the MMR system and MSI is not a major pathway in the carcinogenesis of ICC.

The Expressions of Tyrosine Kinase Receptors, EphA2, c-met and c-erbB-2 in the Human Breast.: Soo Kee Min, Hyun Deuk Cho, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Young Euy Park, Bom Woo Yeom; Korean J Pathol. 2005;39(1):15-22.

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Abstract PDF: BACKGROUND
Tyrosine kinase receptor (TKR) is an important protein for normal-development, growth and tumorigenesis in human tissues. The purpose of this study was to evaluate the effect of TKR in the progression of breast cancer.
METHODS
The expressions of EphA2, c-met and c-erbB-2 were examined, by using immunohistochemical methods and RT-PCR, in samples of breast tissue that included 111 samples of normal epithelium, 34 samples of ductal carcinoma in situ (DCIS), and 109 samples of invasive ductal carcinomas (IDC). The results were compared with the prognostic parameters of breast cancer including the tumor grade, growth pattern, lymph node metastasis and the expressions of ER, PR, p53 and Ki-67.
RESULTS
The protein expressions of the three TKRs were higher in DCIS and IDC than in normal epithelium. The protein expression of EphA2 was correlated with a tumor grade, a labeling index of Ki-67, and the protein expression of c-met. Overexpression of c-erbB-2 was correlated with lymph node metastasis. The mRNA levels of the three TKRs were correlated with each other in normal tissue and IDC. The level of c-met mRNA was higher in the low grade tumors.
CONCLUSIONS
The three TKRs may play roles in the tumorigenesis of human breast cancer. The overexpressions of EphA2 and c-erbB-2 may be a poor prognostic parameter in breast cancers.

Adequate Microsatellite Markers for 1p/19q Loss of Heterozygosity of Oligodendroglial Tumors in Korean Patients.: Se Hoon Kim, Hoguen Kim, Tai Seung Kim; Korean J Pathol. 2005;39(1):23-33.

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Abstract PDF: BACKGROUND
It is well known that oligodendrogliomas can be divided into two groups according to the 1p/19q or 1p loss of heterozygosity (LOH) status because oligodendrogliomas with the 1p/19q LOH or the 1p LOH have a better prognosis and chemosensitivity. In this study, we investigated the adequate microsatellite markers for 1p/19q LOH of oligodendroglial tumors in Korean patients.
METHODS
We performed PCR that was based on the LOH test with the 1p (D1S508, D1S199, D1S2734, D1S186 & D1S312) and 19q (D19S219, D19S112, D19S412 & D19S596) microsatellite markers; these were the markers that were recommended by other researchers. We performed this PCR on microdissected paraffin embedded tissue blocks of 67 tumors from 56 cases.
RESULTS
The PCR based LOH analysis revealed that 3 microsatellite markers (D1S508, D1S2734 & D1S186) of 1p and 2 markers (D19S219 & D19S412) of 19q had higher heterozygosity scores than other markers. In addition, chromosomal LOH status using these selective markers showed a statistically significant difference of prognosis for oligodendroglial tumors.
CONCLUSIONS
We can suggest that the microsatellite markers with high heterozygosity scores (D1S508, D1S2734, D1S186, D19S219 and D19S412) would be adequate microsatellite markers for a PCR based LOH test of oligodendroglial tumors in Korean patients.

Telomerase activity and Expression of MIB-1, Fas and Fas Ligand in Placentas from Women with and without Intrauterine Growth Retardation.: Yi Kyeong Chun, Sung Ran Hong, Moon Ho Yang; Korean J Pathol. 2005;39(1):34-40.

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Abstract PDF: BACKGROUND
The placenta from a pregnancy that is complicated by intrauterine growth retardation (IUGR) tends to be smaller than that from a normal pregnancy. To investigate this difference, we analyzed the telomerase activity, the proliferative activity and the mRNA levels of apoptosis mediators in placentas.
METHODS
In 20 placentas from normal third-trimester pregnancies and 22 placentas form pregnancies that were complicated by IUGR, the telomerase activity was detected by a telomeric repeat amplification protocol assay. The proliferative activity was assessed by immunohistochemical staining using the MIB-1 monoclonal antibody. The expression of the apoptosis mediator was evaluated by semi-quantitative reverse transcription-polymerase chain reactions for fas and fas ligand.
RESULTS
Telomerase activity was detected in 2 (10%) of 20 normal placentas, whereas it was not observed in all tested 13 placentas that were associated with IUGR. The proliferative activity was significantly low in the placentas that were associated with IUGR (7.44+/-2.96%), compared with the normal placentas (11.0+/-3.48%, p=0.002). There was no statistically significant difference in the mRNA levels of fas or fas ligand between two groups.
CONCLUSIONS
Low telomerase and proliferative activities in the placenta may play a role in the pathogenesis of IUGR.

Expressions of p130Cas and FHIT, and Their Relationships with Prognostic Factors for Breast Carcinomas.: Hyun Joo Choi, Ji Han Jung, Jinyoung Yoo, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2005;39(1):41-47.

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Abstract PDF: BACKGROUND
BCAR1/p130Cas protein is the human homologue of rat p130Cas protein, and it is a docking protein involved in the intracellular signaling pathways. This protein also causes the proliferating human breast cancer cells to be resistant to antiestrogen drugs. The fragile histidine triad (FHIT) protein is presumed to have a tumor suppressor function in a number of human tumors. The aim of this study was to investigate expressions of p130Cas and FHIT in breast carcinomas and to evaluate their relationship with the clinicopathological prognostic factors.
METHODS
A total of 93 cases of invasive breast carcinomas was retrospectively reviewed. The expressions of p130Cas and FHIT were examined by immunohistochemical methods.
RESULTS
p130Cas expression was observed in all breast carcinomas: p130Cas immunoreactivity was strongly positive in 39 cases (41.9%), moderately positive in 49 cases (52.7%) and weakly positive in 5 cases (5.4%) of 93 cases. It was statistically correlated with the p53 (p=0.035) and c-erbB-2 (p=0.024) expressions. The FHIT protein expression was markedly reduced or completely negative in 59 cases (63.4%), but it was not correlated with the clinicopathological prognostic factors. There was no significant correlation between p130Cas and FHIT expressions.
CONCLUSIONS
This study seems to provide meager information on whether these proteins may be useful prognostic factors, and so this topic needs further study.

Case Reports

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: A Report of Two Cases.: Young Ran Shim, Young Kyung Bae, Joon Hyuk Choi, Mi Jin Kim, Won Hee Choi; Korean J Pathol. 2005;39(1):48-53.

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Abstract PDF: Cribriform-morular variant of papillary thyroid carcinoma is an unusual and peculiar subtype of papillary thyroid carcinomas. It occurs both sporadically and in association with familial adenomatous polyposis. We report here on two cases of cribriform-morular variant of papillary thyroid carcinoma in a 33-year-old woman and in a 21-year-old woman. On gross examination, both cases were multicentric. The first case showed two well-encapsulated yellow solid masses in the right (2.0 cm) and the left lobes of the thyroid gland (0.5 cm). The second case showed four well-encapsulated gray-white solid lobulating masses and nodules in the right (4.5 and 1.2 cm) and the left lobes (1.1 and 0.8 cm) of the thyroid gland. Microscopically, both cases exhibited an intricate blending of papillary, cribriform, trabecular, spindle, and solid patterns of growth with morular areas. Typical nuclear features of papillary carcinomas were focally seen. Immunohistochemically, the tumor cells were positive for thyroglobulin, thyroid transcription factor-1 (TTF-1), and beta-catenin, but were negative for calcitonin.

Inflammatory Myofibroblastic Tumor of the Breast: A Case Report.: Myoung Ja Chung, So Yeong Oh, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 2005;39(1):54-58.

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Abstract PDF: Inflammatory myofibroblastic tumor (IMT) is characterized by a clonal proliferation of myofibroblasic spindle cells, and this is accompanied by a lymphoplasmacytic infiltration. In the majority of cases, this disease has occurred in the lungs and only 9 cases of IMT in the breast have been previously reported. We report here on an IMT in a 25-year-old-female who presented with a palpable mass in the right breast. Histologically, it was characterized by plump spindle cells admixed with prominent inflammation, that was composed of lymphocytes and plasma cells. Immunohistochemically, the spindle cells were positive for vimentin and -smooth muscle actin.

Adenomyoma of Ampulla of Vater or the Common Bile Duct: A Report of Three Cases.: Kee Taek Jang, Jin Seok Heo, Seoung Ho Choi, Dong Il Choi, Jae Hoon Lim, Young Lyun Oh, Geung Hwan Ahn; Korean J Pathol. 2005;39(1):59-62.

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Abstract PDF: Adenomyoma is a rare non-neoplastic lesion of the biliary tract. Here we report on three cases of adenomyoma; one located in the ampulla of Vater and two located in the common bile duct. Although preoperative endoscopic and radiological evaluations could not determine whether lesions were benign or malignant, intra-operative frozen section histologic examinations aided the differential diagnosis. Microscopic features of a lobular gland architecture with basally located nuclei and the absence of desmoplastic stromal reaction were found to be characteristic in frozen and paraffin sections.

Diffuse Leiomyomatosis of the Uterus: A Brief Case Report.: Su Jin Kim, Mee Sook Roh; Korean J Pathol. 2005;39(1):63-65.

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Abstract PDF: Diffuse leiomyomatosis of the uterus is a rare condition that is distinguished from the uterine leiomyoma due to the diffuse involvement of the myometrium by numerous, ill-defined, smooth muscle nodules. We present here a case of diffuse uterine leiomyomatosis in a 34-year-old woman. The hysterectomy revealed a symmetrically enlarged uterus containing numerous, small, ill-defined leiomyomatous nodules. Microscopically, the nodules were composed of compact fascicles and interweaving bundles of uniform benign smooth muscle cells. On the immunohistochemical staining, the progesterone receptor level was higher in the leiomyomatosis than in the adjacent normal myometrial tissue, but the estrogen receptor level and Ki-67 labeling index were equal in both areas. At the twelve months follow-up, this patient has been doing very well with no evidence of pelvic or intraabdominal recurrence of disease.

Solitary Schwannoma of the Breast: A Case Report.: Jung Uee Lee, Hae Joung Sul, Byoung Jeon Park; Korean J Pathol. 2005;39(1):66-68.

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Abstract PDF: Schwannomas arise from the neural crest-derived Schwann cells. Their most common locations are the extremities, neck, mediastinum, retroperitoneum, and cerebellopontine angle. They have rarely been reported to occur in the breast. We herein report on a case of schwannoma of the breast in a 30-year-old woman. The ultrasonographic examination showed a well defined ovoid hypoechoic mass in the upper outer quadrant of her left breast. A presumptive diagnosis of fibroadenoma was made, and the mass was then removed. The histopathologic and immunohistochemical features confirmed the diagnosis of schwannoma of the breast.

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