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Volume 42(1); February 2008
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Original Articles
Protein Expression and Gene Amplification of Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer: Correlation with the Response to Gefitinib Therapy.
Jinyoung Yoo, Kyungji Lee, Ji Han Jung, Byoung Yong Shim, Sung Hwan Kim, Deog Gon Cho, Myeong Im Ahn, Chi Hong Kim, Kyu Do Cho, Hoon Kyo Kim, Seok Jin Kang
Korean J Pathol. 2008;42(1):1-8.
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AbstractAbstract PDF
BACKGROUND
Gefitinib is an EGFR tyrosine kinase inhibitor that has shown dramatic effectiveness in a subset of non-small cell lung cancer (NSCLC) patients. We evaluated the response rate to gefitinib, and the significance of the EGFR and HER2/neu status as predictive markers of the tumor response.
METHODS
The EGFR and HER2/neu protein expressions, as determined by immunohistochemistry (IHC) and gene amplification via chromogenic in situ hybridization (CISH), were analyzed in biopsy specimens from 46 patients with advanced NSCLC. After their failure with the first-line treatment, all the patients had received gefitinib treatment.
RESULTS
A partial response (PR) was achieved in 8 patients (17.4%). An EGFR overexpression was detected in 80.4% (37/46) of the tumors, and this was observed exclusively in patients with a PR (100% vs 75.3%, respectively; p=0.076). EGFR gene amplification was present in 47.8% of the tumors (22/46). HER2/neu was overexpressed in 13%(6/46) and it was amplified in 17% (7/46). The overall survival was prolonged in the female patients (p=0.007), and in patients with T1 and T2 disease (p=0.039), adenocarcinoma (p=0.010), a PR (p=0.022), an EGFR IHC+ status (p=0.033), an EGFR IHC+/CISH+ status (p=0.010), or an EGFR+/HER2/neu+ status (p=0.030). On multivariate analysis, gender, T disease and EGFR IHC/CISH remained the significant predictors of survival.
CONCLUSIONS
Gefitinib showed a modest effect for the patients with chemotherapy-refractory advanced NSCLC. A combination of EGFR IHC and CISH might be important for identifying those patients who are most likely to benefit from gefitinib therapy.
Inactivation of TPEF Gene by Aberrant Methylation in Hepatocellular Carcinoma.
Woon Bok Chung, Soon Young Kim, So Young Chun, Ku Seong Kang, Hae Ahm Lee, Joung Ok Kim, Ji Young Park, Yoon Kyung Sohn, Jung Wan Kim
Korean J Pathol. 2008;42(1):9-15.
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AbstractAbstract PDF
BACKGROUND
Abnormalities of genomic methylation patterns have been shown to play a role in the development of carcinoma, and the silencing of tumor suppressor genes is related to local de novo methylation.
METHODS
Using methylation specific arbitrarily primed-Polymerase Chain Reaction (Ms AP-PCR), we identified a 322 bp sequence that contained a 5' un-translated and exon1 regions of the TPEF gene. To evaluate the inactivation of the TPEF gene through hypermethylation in hepatocellular carcinoma (HCC), we investigated the correlation between methylation patterns and TPEF expression in tumor tissues of human HCC and cell lines via a Combined Bisulfite Restriction Assay (CoBRA) and RT-PCR.
RESULTS
A dense methylation pattern of the TPEF was detected in most cell lines, as well as in 10 of the 14 (71.4%) HCC tissues. In addition, loss of heterozygosity (LOH) from the TPEF gene was observed in 5 of the 14 (36%) HCC tissues. Furthermore, RT-PCR analysis revealed TPEF expression in 5 of 8 (62.5%) cell lines. Finally, treatment with a demethylating agent, 5-Aza- 2'-deoxycitidine (5-AzaC), increased the expression of TPEF mRNA.
CONCLUSION
These results indicate that inactivation of the TPEF gene through hypermethylation may be a mechanism by which tumorigenesis occurs in HCC.
Diffuse Large B Cell Lymphoma Shows Distinct Methylation Profiles of the Tumor Suppressor Genes among the Non-Hodgkin's Lymphomas.
Sun Och Yoon, Young A Kim, Yoon Kyung Jeon, Ji Eun Kim, Gyeong Hoon Kang, Chul Woo Kim
Korean J Pathol. 2008;42(1):16-20.
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AbstractAbstract PDF
BACKGROUND
Aberrant methylation of CpG islands in promoter regions is one of the major mechanisms for silencing of tumor suppressor genes in various types of human cancers including non-Hodgkin's lymphomas (NHL). In this study, we investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in NHLs and compared the methylation profiles between B-cell and T/NK-cell NHLs.
METHODS
54 cases of B-cell NHLs and 16 cases of T/NK-cell NHLs were examined for the methylation status of eight genes using methylation specific PCR.
RESULTS
CpG islands methylation was variously found in eight genes as follows; DAPK (71%), MT1G (70%), p16 (53%), CDH1 (53%), THBS1 (56%), MGMT (27.1%), COX2 (13%), and RUNX3 (11.4%). In six cases (8 %), methylation was not observed in any of these genes. Overall methylation index of B-cell NHLs (0.48) was significantly higher than that of T/NK-cell NHLs (0.32). Of eight genes tested, THBS1 and CDH1 methylations were much more prominent in diffuse large B-cell lymphomas than in T/NK-cell NHLs or other B-cell NHLs.
CONCLUSION
This study suggests that aberrant CpG island methylation is a frequent event in NHLs, and diffuse large B-cell lymphomas show overlapping but distinct methylation profiles.
The Utility of HMW-CK and CK5/6 Immunohistochemical Stains for Differentiating Ductal Proliferative Lesions and Ducal Carcinoma of the Breast.
Sung Hee Son, Ju Yeon Song, Hye Kyoung Yoon
Korean J Pathol. 2008;42(1):21-26.
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AbstractAbstract PDF
BACKGROUND
Basal-type cytokeratins may help to distinguish benign from malignant intraductal proliferative lesions. The basal-type cytokeratins expression is markedly decreased or absent in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC). However, the expression patterns vary according to the antibodies that are used for staining.
METHODS
HMW-CK (clone 34 E12) was applied to 175 lesions, and CK5/6 (clone D5/16B4) was applied to 145 lesions. The specimens were IDC (n=165), DCIS (n=35), ADH (n=37), florid ductal hyperplasia (FDH) (n=38) and columnar cell lesion (CCL) (n=45). The expression patterns of HMW-CK and CK5/6 were categorized as negative, focal positive and positive.
RESULTS
Loss of the HMW-CK expression was noted in 76% (66/87) of the IDC, 78% (21/27) of the DCIS, 78% (21/28) of the ADH, and 55% (10/18) of the FDH. Loss of the CK5/6 expression was found in 96% (75/78) of the IDC, in all the DCIS (n=8) and ADH (n=9), and in none of the FDH (n=20). Loss of the CK5/6 expression is more reliable than that of the HMW-CK expression for differentiating FDH, ADH and malignant intraductal proliferatve lesions. Eleven (73%) of 15 CCLs revealed the loss of the HMW-CK expression, but all the CCLs (n=30) were negative for CK5/6 (p=0.0161).
CONCLUSION
CK5/6 antibody is more reliable than HMW-CK antibody for differentiating FDH from ADH or DCIS, and for discriminating CCL.
DNA Copy Number Changes in Thyroid Medullary Carcinomas Determined by Comparative Genomic Hybridization.
Hyun Jung Kim, Kowan Ja Jee, Young Khee Shong, Suck Joon Hong, Gyungyub Gong
Korean J Pathol. 2008;42(1):27-32.
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AbstractAbstract PDF
BACKGROUND
A point mutation in the RET proto-oncogene, in medullary thyroid carcinoma (MTC) is well known, but no other genetic causes of MTC have been found. This study was performed to identify the most common DNA copy number changes in MTC by comparative genomic hybridization (CGH).
METHODS
Twenty-nine surgically resected MTC specimens were retrospectively selected from patients operated on between 1996 and 2004 at the Asan Medical Center. A review of the clinical data and pathological findings was performed. Congored staining and immunohistochemical stains (calcitonin, chromogranin A and CEA) were processed by tissue microarray. CGH analysis was performed.
RESULTS
The Congo-red stain was positive in only 12 cases. The immunohistochemical results were positive in 29 cases for chromogranin A, 26 cases for CEA and 25 cases for calcitonin. DNA copy number changes were found in 23 cases (79.3%). The most frequent change was a gain of 19q (65.5%); less frequent changes were gain of 22 (55.2%), 19p (51.7%), 16p (27.58%), 17q (17.24%), and loss of 4q (27.6%) and 3p (17.24%).
CONCLUSIONS
DNA copy number changes of MTC were more common (79.3%) than reported in previous studies. The most frequent changes were gains in 19q, 22 and 19p.
Case Reports
Adenocarcinoma Arising from Heterotopic Gastric Mucosa in Cervical Esophagus: A Case Report.
Young Ok Hong, Jeong Eun Hwang, In Chul Lee, Jin Hyuk Lee, Seung Il Park, Kyung Ja Cho
Korean J Pathol. 2008;42(1):33-36.
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AbstractAbstract PDF
Heterotopic gastric mucosa (HGM) of the upper esophagus, referred as "cervical inlet patch (CIP)", is a benign lesion that is present in 3.8-10% of the adult population. Adenocarcinomas arising from HGM of the upper esophagus are exceedingly rare. The authors report one additional case of histologically confirmed adenocarcinoma arising from a CIP. The patient had concomitant primary adenocarcinoma of the colon. The right hemicolectomy specimen and total esophagectomy specimen after preoperative chemoradiotherapy showed histologically different adenocarcinomas. The residual esophageal tumor was characterized by large mucin pools, fibrous septa, and floating tumor cells. HGM of both the fundic and antral types was seen on the surface and sides of the tumor. The independent origins of the two cancers were confirmed by immunohistochemical studies for cytokeratins 7 and 20. Without further treatment, the patient remained free of disease after 29 months of follow-up.
Primary Pulmonary Glomus Tumor, Diagnosed by Preoperative Needle Biopsy: Report of One Case and Literature Review.
Mi Jin Kim, Woo Jung Sung
Korean J Pathol. 2008;42(1):37-40.
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AbstractAbstract PDF
Glomus tumors commonly occur in dermal and subcutaneous tissue in the subungal region of a finger. Some glomus tumors occur extracutaneously, including lung. Only 15 cases of primary pulmonary glomus tumor have been described in literature. In this report, we describe a case of primary pulmonary glomus tumor, which is the first case diagnosed before surgical resection. A 51-year-old man underwent a needle biopsy of a well defined coin-like mass in left lower lobe of the lung on chest radiography. Microscopic examination revealed a tumor composed of perivascularly arranged round to ovoid epithelioid cells with abundant eosinophilic cytoplasm. Tumor cells are immunoreactive for smooth muscle actin and vimentin, but negative for desmin, cytokeratin (AE1/AE3), chromogranin, or synaptophysin. A diagnosis of glomus tumor was then made. The lung mass was resected by wedge resection after being diagnosed by preoperative lung needle biopsy. Although primary pulmonary glomus tumor is rare, most cases follows a benign course. For proper treatment of the patient, glomus tumor should be considered as a differential diagnosis of solitary lung mass.
Combined Xanthogranulomatous Urachitis and Bullous Cystitis: A Case Report.
Ji Eun Kwak, Han Seong Kim, Mee Joo, Sun Hee Chang, Sang Hwa Shim, Je G Chi, In Rae Cho
Korean J Pathol. 2008;42(1):41-44.
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AbstractAbstract PDF
Xanthogranulomatous inflammation of the urachus is a very rare benign chronic inflammatory disease of an unknown etiology. Herein we report a case of a 31-year-old woman who complained of lower abdominal pain and dysuria. Cystoscopy revealed a bullous change at the dome of the urinary bladder. MRI revealed a cystic mass above the bladder dome that extended to the umbilicus. A partial cystectomy with urachal resection was performed. Pathological examination revealed xanthogranulomatous urachitis combined with bullous cystitis.
Gliosarcoma with Components of Anaplastic Oligodendroglioma and Unclassifiable Spindle Cells: A Case Report.
Jung Woo Choi, Youngseok Lee, Jung Suk An, Nam Hee Won, Yong Gu Chung, Yang Seok Chae
Korean J Pathol. 2008;42(1):45-49.
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AbstractAbstract PDF
Gliosarcoma is a distinct disease entity that is characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. The tumor in our case was a rare morphologic variant of gliosarcoma with components of anaplastic oligodendroglioma and unclassifiable spindle cells. Spindle cells showed CD34 and S-100 protein immunoreactivity, which was possibly related to peripheral nerve sheath differentiation. This unique feature has not been described previously and so this case expands the spectrum of possible divergent mesenchymal differentiation, and it lends support to pluripotential stem cells being the origin of this tumor.
Actinomycosis of the Penile Shaft Coexisting with Fibrous Pseudotumor of the Testis.
Eun Jung Cha, Kyu Yun Jang, Ho Sung Park, Jong Kwan Park, Chang Seop Lee, Myoung Ja Chung, Woo Sung Moon, Dong Geun Lee, Myoung Jae Kang
Korean J Pathol. 2008;42(1):50-53.
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AbstractAbstract PDF
Here, we present an uncommon case of the penile shaft actinomycosis with coexisting fibrous pseudotumors of the testis. A 37-year-old, circumcised man presented with one penile and eight scrotal masses. The penile mass having a healed surface ulceration was located at the right side of the penile shaft. It was relatively circumscribed without a fibrous capsule. The cut surface showed a yellow-brown color with central focal necrosis. The scrotal tumors were circumscribed, whorled, white masses 0.3-2.0 cm in diameters, and were attached to the tunica vaginalis and tunica albuginea. Microscopically, the penile mass showed active inflammatory changes containing actinomyces displaying characteristic sulfur granules. Testicular masses were fibrous pseudotumors composed of bland spindle and stellate cells lying in dense collagenous stroma. Actinomycosis of the penis has been reported to occur at the corona of the uncircumcised penis associated with pilonidal sinus. The present case was not associated with pilonidal sinus and, unusually, displayed co-existence with fibrous pseudotumors of the testis.
Mucinous Tubular and Spindle Cell Carcinoma of Kidney Occurring in a Patient with Pulmonary Adenocarcinoma.
Seog Yun Park, Gyeong Hoon Kang, Jae Y Ro, Jennifer Black, Jinsoo Chung, Kang Hyun Lee, Eun Kyung Hong, Weon Seo Park
Korean J Pathol. 2008;42(1):54-59.
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AbstractAbstract PDF
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that has only been recently described. Furthermore, a case of MTSCC associated with a simultaneous lung cancer in the same patient has never been reported in the literature. In this paper, we describe a kidney tumor that was detected during staging work-up in a 72-year-old lung cancer patient. The kidney tumor was removed and shown to exhibit histological and immunophenotypic features of MTSCC, completely distinct from the pulmonary adenocarcinoma. In addition, this case was unique because it was characterized by neuroendocrine differentiation as well as p53 and Ki-67 overexpression in tumor cells. Therefore, we report a case of MTSCC diagnosed in a patient with pulmonary adenocarcinoma and describe the detailed histologic and immunohistochemical features of MTSCC.
Mucinous Adenocarcinoma in a Horseshoe Kidney.
Man Hoon Han, Sang Chul Nam, Bup Wan Kim, Ghil Suk Yoon
Korean J Pathol. 2008;42(1):60-62.
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AbstractAbstract PDF
We report here on a case of mucinous adenocarcinoma that probably originated in the renal pelvis of a horseshoe kidney. A 61-year-old woman presented with a palpable mass in the left upper quadrant of the abdomen, and this mass had been present for several months. Computed tomography (CT) revealed a left renal pelvic tumor in the horseshoe kidney. Grossly, a 10x9x8 cm unilocular cystic mass filled with chocolate colored mucinous fluid was seen. A connection between the cystic mass and the renal pelvis was demonstrated on retrograde pyelography. Microscopically, the cyst contained anaplastic columnar mucosecretory epithelial cells. Some atypical cell clusters were freely floating in the mucinous lakes. The histopathological findings were consistent with mucinous adenocarcinoma. In addition, glandular metaplasia was noted in the cystic wall. Immunohistochemical assessment of the pelvic adenocarcinoma revealed the positive expressions of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) and a weak positive expression of cytokeratin 7 (CK7).
Adenocarcinoma of the Sigmoid Colon with Prominent Rhabdoid Features: A Case Report.
Hoon Kyu Oh, Chang Ho Cho, Yoon Seup Kum
Korean J Pathol. 2008;42(1):63-65.
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AbstractAbstract PDF
Colorectal adenocarcinoma with rhabdoid features is extremely rare and only two cases have been previously reported. We report here on a case of colorectal adenocarcinoma with prominent rhabdoid features in a 69-year-old female. The specimen was an ulcerative mass from the sigmoid colon, and it measured 3.5x3 cm. Microscopic examination of the tumor showed mostly rhabdoid cells that had eccentrically located large nuclei and foci of glandular formation. A transitional area from the poorly differentiated adenocarcinoma to the rhabdoid tumor was also noted. Immunohistochemical studies showed strong reactivity of the glandular forming cells for pan-cytokeratin, and the cells were occasionally positive for vimentin. The cells with rhabdoid features were diffusely positive for vimentin and focally positive for pan-cytokeratin. These results suggested that the cells with rhabdoid features originated from dedifferentiated primary adenocarcinoma. Since colorectal adenocarcinoma with rhabdoid features is highly aggressive and unresponsive to conventional therapy, making the preoperative diagnosis is important to facilitate the treatment.

JPTM : Journal of Pathology and Translational Medicine