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Volume 43(5); October 2009
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Editorial
Molecular Biologic Techniques in Cytopathologic Diagnosis.
Tae Sook Hwang
Korean J Pathol. 2009;43(5):387-392.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.387
  • 3,406 View
  • 39 Download
  • 9 Citations
AbstractAbstract PDF
Molecular diagnosis is an application of the knowledge on molecular mechanisms of disease to diagnosis, therapeutic decision-making, and prognostication. Basically any molecular diagnostic technique could be used in molecular diagnostic cytopathology. Currently applicable molecular techniques in the cytopathology field include PCR based molecular techniques (SSCP, DHPLC, RFLP, LOH, MSI, RT-PCR, QRT-PCR, allele-specific PCR, sequencing, and methylation analysis), FISH, cDNA microarray, aCGH, and reverse-phase protein microarray, etc. Exfoliative cytology as well as fine needle aspiration cytology specimen can be used for analysis. In order to obtain a successful result, collection of target cells without contamination of the blood cells, inflammatory cells including histiocytes, and stromal cells, and a good DNA yield are most important. Molecular diagosis finds its full meaning when interpreted by those who can combine the clinical background of the disease with morphological, immunocytochemical, and molecular diagnostic results. Therefore, these assays would fulfill their full potential when interpreted by the cytopathologists.
Original Articles
Enhanced Protein Expression of Signal Transducer and Activator of Transcription 3 and Protein Kinase Substrate p36 in Hepatocellular Carcinoma.
Hongxiu Han, Si Hyong Jang, Chan Kum Park
Korean J Pathol. 2009;43(5):393-399.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.393
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AbstractAbstract PDF
BACKGROUND
Signal transducers and activators of transcription 3 (STAT3) and protein kinase substrate p36 may be involved in cell proliferation, differentiation and growth.
METHODS
Immunohistochemistry for STAT3 and p36 was performed in 46 patients with hepatocellular carcinoma (HCC).
RESULTS
STAT3 staining was present in the cytoplasm and/or nucleus, while p36 staining was present in the nucleus. STAT3 and p36 expression occurred in 78.3% (36/46) and 47.8% (22/46) of HCC patients, respectively. However, no correlation was found between STAT3 and p36 protein expression (p>0.05). Enhanced expression of STAT3 was negatively correlated with portal vein invasion (p=0.033). Expression of STAT3 in the nucleus was correlated with tumor grade (p=0.004). Enhanced expression of p36 was correlated with tumor grade (p=0.031). HCC was correlated with HBV infection (p=0.032). The patients'5-year survival was related to expression of p36 (p=0.044), but not to total STAT3 or nuclear STAT3 (p>0.05).
CONCLUSIONS
The enhanced expression of STAT3 in the nucleus and the enhanced expression of p36 are associated with the aggressive phenotype of HCC. Enhanced p36 expression may contribute to poor survival of patients with HCC.
The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal beta-catenin Expression in Lobular Carcinoma.
Gwangil Kim, Ji Young Kim, Hee Jung An, Haeyoun Kang, Tae Heon Kim, Jung Yon Shim, Jin Hyung Heo, Hai Lin Park, Young Kil Choi
Korean J Pathol. 2009;43(5):400-407.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.400
  • 2,472 View
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
APC and E-cadherin are the key molecules in the Wnt/beta-catenin pathway. We attempted to define the epigenetic alteration of APC and CDH1 (the E-cadherin gene) and the expression of Wnt-related molecules in human mammary carcinomas.
METHODS
Sixty-four mammary carcinomas, including 52 invasive ductal carcinomas (IDCs) and 12 invasive lobular carcinomas (ILCs), were evaluated using methylation-specific PCR and immunohistochemistry. We performed immunohistochemistry for E-cadherin, beta-catenin, APC, Wnt1, cyclin D1, ER, PR and C-erb B2.
RESULTS
Hypermethylation of APC and CDH1 was observed in 38 (59%) and 28 (44%) cases, respectively. CDH1 hypermethylation in ILCs was increased compared to that in IDCs (p=0.002) and it was associated with the loss of E-cadherin (p=0.02) and beta-catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of beta-catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or beta-catenin expression was markedly decreased compared to that in IDCs (p<0.001 in both).
CONCLUSIONS
Methylation of APC or CDH1 was relatively frequent in mammary carcinomas. The loss of E-cadherin in mammary carcinoma was associated with CDH1 methylation, and abnormal beta-catenin expression was related to the loss of E-cadherin in ILC.
Significance of the Expression of Cathepsins B, H, & L in Colonic Epithelial Neoplasms.
Jae Young Sim, Mi Ja Lee, Keun Hong Kee
Korean J Pathol. 2009;43(5):408-412.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.408
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AbstractAbstract PDF
BACKGROUND
Cathepsin is associated with tumorigenesis, tumor invasion and metastasis through its ability to induce degradation of extracellular matrix components.
METHODS
To investigate the correlation between cathepsin expression and tumor progression, invasion depth or nodal metastasis, immunohistochemical staining for cathepsins B, H and L were done on 20 hyperplastic polyps, 48 adenomas, and 67 adenocarcinomas of the colon. Evaluation of the expression of cathepsins B, H and L was based on the percentage of neoplastic cells that stained positive for any given cathepsin.
RESULTS
Cathepsin B expression was significantly higher in adenocarcinomas than adenomas (29.33 vs 5.48%), but was not associated with the degree of differentiation, depth of invasion and nodal status of the tumors. Expression of cathepsins H and L was absent or low in both adenomas and adenocarcinomas. CONCLUSIONS: We suggest that cathepsin B is involved in progression of a subset of colonic adenomas, while cathepsins H and L are not.
The EGFR Protein Expression and the Gene Copy Number Changes in Renal Cell Carcinomas.
Sangho Lee, Jungsuk An, Aeree Kim, Young Sik Kim, Insun Kim
Korean J Pathol. 2009;43(5):413-419.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.413
  • 2,613 View
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
The epidermal growth factor receptor (EGFR) is known to be involved in many tumor promoting activities. EGFR inhibition has been tried as a therapeutic modality in many human malignancies.
METHODS
The expression of EGFR protein and the gene copy number changes were studied in 135 clear cell carcinomas and 16 papillary renal cell carcinomas (RCCs), and these tumors were diagnosed between 1995 and 1997.
RESULTS
An EGFR protein expression (2+ and 3+) was found in 54.1% of the clear cell RCCs and in 43.8% of the papillary RCCs. In the clear cell RCCs, its expression was associated with male gender, the tumor size (> or =4 cm) and high T stages (T2 and T3), with statistical significance. Trisomy and polysomy of the EGFR gene were found in 27 (25.7%) and 40 (38.1%) of 105 clear cell RCCs, respectively. Trisomy and polysomy were correlated with an EGFR protein expression and a high clinical T stage, with statistical significance. Among 15 papillary RCCs, 13 tumors showed trisomy (86.7%) and one showed polysomy (6.7%). Amplification was not found in both the clear cell and papillary type RCCs.
CONCLUSIONS
A considerable numbers of RCCs showed an overexpression of EGFR protein and increased EGFR gene copy numbers, yet the clinical significance of conducting a FISH study in RCC patients seems to be limited.
DNA Methylation Profiles of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 in B-Cell Lymphomas.
Sung Sun Kim, Young Hyo Choi, Chang Woo Han, Yoo Duk Choi, Youngkyu Park, Je Jung Lee, Hyeoung Joon Kim, Il Kwon Lee, Ji Shin Lee, Sang Woo Juhng, Chan Choi
Korean J Pathol. 2009;43(5):420-427.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.420
  • 2,964 View
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
This study was designed to examine the prevalence of aberrant promoter methylation in a selected panel of genes potentially involved in lymphoid tumors.
METHODS
The promoter hypermethylation status of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 was measured by methylation-specific PCR for 82 cases of B-cell lymphoma. Immunohistochemical staining using MGMT and SHP1 antibodies was conducted on 43 out of 82 cases.
RESULTS
The number of MGMT aberrant methylations was lower in diffuse large B-cell lymphoma (DLBCL) than in other malignant lymphomas. The methylation of DAPK1 was frequently detected in follicular lymphoma (FL), marginal zone B-cell lymphoma (MZL) and DLBCL. With one exception, methylation of hMLH1 was not observed in B-cell lymphomas. The methylation frequency of CDH1, and HIC1 was similar in B-cell lymphomas. However, the methylation of SHP1 gene was more frequently observed in cases of FL, DLBCL, and MZL than in chronic lymphocytic lymphoma. MGMT and SHP1 promoter methylation were inversely correlated with the protein expression observed upon immunohistochemical staining.
CONCLUSIONS
Aberrant promoter methylation of multiple genes occurs with variable frequency throughout the B-cell lymphomas, and methylation of hMLH1 is rarely observed in B-cell lymphomas.
Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability.
Sang Kyum Kim, Junjeong Choi, Hyun Ki Kim, Young Nyun Park, Si Young Song, Hoguen Kim
Korean J Pathol. 2009;43(5):428-434.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.428
  • 2,526 View
  • 29 Download
  • 1 Citations
AbstractAbstract PDF
BACKGROUND
High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production. However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes.
METHODS
We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes.
RESULTS
MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013). We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs.
CONCLUSIONS
These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.
Predictive Significance of KRAS and Tau for Chemoresponse in Advanced Non-Small-Cell Lung Cancer.
Jinyoung Yoo, Byoung Yong Shim, Chang Young Yoo, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2009;43(5):435-440.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.435
  • 2,633 View
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Taxane-platinum combinations are often used as first-line treatments for patients with advanced non-small cell lung cancer (NSCLC). Response to chemotherapy for these patients is still poor. The aim of our study was to investigate, for this disease, whether KRAS and Tau proteins affect responses to taxane-platinum combinations.
METHODS
Expression of KRAS and Tau was examined immunohistochemically in 71 tumor samples obtained from patients with stage IIIB or IV NSCLC prior to combination therapy. Expression was correlated with tumor responses.
RESULTS
The response rate was 55% (39 of 71). KRAS and Tau were expressed in seven (10%) and 31 (44%) patients, respectively. All seven KRAS-positive patients were non-responders (p=0.014). Among Tau-positive patients, 35% (11 of 31) responded to therapy, whereas a partial response was observed in 70% (28 of 40) of Tau-negatives (p=0.045). Two were positive for both, and they were non-responders. In patients negative for both, the response rate was 71% (25 of 35) (p=0.012).
CONCLUSIONS
Expression of KRAS and Tau are significantly correlated with poor responses to this combination therapy in advanced NSCLC patients, and may be a useful marker for chemoresistance.
Clinicopathologic Characteristics of Endometrial Adenocarcinomas in Young Women.
Gawon Choi, Jeong Won Kim, Shin Kwang Khang, Kyu Rae Kim
Korean J Pathol. 2009;43(5):441-447.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.441
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AbstractAbstract PDF
BACKGROUND
Despite an increased incidence of endometrial carcinomas in young Korean women, clinicopathologic characteristics and treatment outcomes have not been analyzed.
METHODS
We investigated clinicopathologic characteristics of endometrial carcinoma in 48 women who were under the age of 40 in order to determine treatment guideline.
RESULTS
According To The Criteria Of The Korean Society For Obesity, 70.8% Of Study Patients Were Overweight Or Obese, With An Average Body Mass Index (Bmi) Of 26.0 kg/m2. Twelve Patients Received Progesterone Treatment Only, And 6 Of Them Later Had Successful Pregnancies. The Histologic Subtype Was Endometrioid Adenocarcinoma In All Patients. Figo Stages Were 1A(41.7%), 1B(47.1%), II (2.8%), IIB2.8%), IIIA(2.8%), And IIIC (2.8%). Figo Grades Were Grade 1 (79%) Or 2 (21%). The Average Depth Of Invasion, Excluding Stage 1a, Was 4.6 Mm In The Hysterectomy Specimens. Two Patients Were Given Post-operative Radiation Treatment And 4 Were Treated With Chemotherapy. All But One Case Had An Uneventful Postoperative Course During Follow-up.
CONCLUSIONS
A majority of endometrial carcinomas in young Korean women were associated with an early FIGO stage, favorable histologic subtype and grades, and a good prognosis. Progesterone treatment with close observation was a successful treatment option in a selected group of young patients.
Comparison of Cytologic Evaluation between Conventional Method and CellprepPlus(R) Liquid-Based Cytology in Body Fluid.
Ji Hae Koo, Ho Chang Lee, Hyung Geun Song, Hye Suk Han, Ki Hyeong Lee, Kang Hyeon Choe, Ki Man Lee, Ok Jun Lee
Korean J Pathol. 2009;43(5):448-452.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.448
  • 3,657 View
  • 86 Download
  • 5 Citations
AbstractAbstract PDF
BACKGROUND
Assessment of body fluid cytology is a useful means of evaluating a metastatic tumor. Liquid-based cytology (LBC) has been developed as a replacement for the conventional Papanicolaou (CP) test. This study was performed to compare CellprepPlus(R) LBC with CP in cytologic diagnosis. METHODS: Body fluid samples (n=188, including 72 peritoneal fluid and 116 pleural fluid samples) were divided equally and analyzed by both CellprepPlus(R) and CP.
RESULTS
CellprepPlus(R) revealed distributed thin layers of non-overlapping cells. All CellprepPlus(R) preparations were adequate, while 18 (9.57%) CP preparations were inadequate. The respective diagnostic rates of CellprepPlus(R) and CP were 75.0% and 76.1% negative, 10.6% and 6.38% atypical, 5.85% and 2.66% suspicious, and 8.51% and 5.32% malignant. Of the 58 confirmed cases, the sensitivity of CellprepPlus(R) and CP was 94.4% and 73.3%, respectively, and the negative predictive value was 97.2% and 87.9%, respectively.
CONCLUSIONS
CellprepPlus(R) LBC has better sensitivity and negative predictive value, and produces higher quality slide preparations than than CP, making it suitable as in screening of body fluid as a cytologic diagnostic tool.
Histologic Correlation of Atypical Glandular Cells in Cervical Smears.
Yi Kyeong Chun, Sung Ran Hong, Hye Sun Kim, Ji Young Kim, Hy Sook Kim
Korean J Pathol. 2009;43(5):453-457.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.453
  • 2,689 View
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  • 3 Citations
AbstractAbstract PDF
BACKGROUND
The study evaluated the histologic correlation and clinical significance of atypical glandular cells (AGC) detected either on conventional smears (CS) or liquid-based cytology (LBC).
METHODS
Two hundred and seventy-seven (0.11%) of 261,925 cervical smears were interpreted as AGC by the Bethesda system 2001 from January 2006 to December 2008. Cytohistological correlation was performed on 192 cases.
RESULTS
The prevalence of AGC was 0.07% and 0.13% for CS and LBC smears, respectively. Distribution of AGC subcategories were as follows: atypical endometrial cells 53.8%, atypical endocervical cells 22.7%, atypical glandular cells 19.5%, atypical endocervical cells favoring neoplasia 2.2%, and atypical glandular cells favoring neoplasia 1.8%. Fifty-nine (27.4%) of 192 patients were confirmed as having clinically significant lesions comprising endometrial adenocarcinoma (12.5%), endometrial hyperplasia (6.0%), cervical adenocarcinoma (2.3%), high-grade squamous intraepithelial lesion (HSIL) (1.9%), low-grade SIL (1.9%), adenocarcinoma in situ (1.4%), or ovarian metastasis (1.4%).
Conclusion
Compared with CS, LBC was presently associated with a higher prevalence of AGC. Histologic follow-up showed a very low HSIL rate compared to other studies. Endometrial adenocarcinoma was the most common malignant lesion detected because of increasing prevalence of endometrial adenocarcinoma, concentration on endometrial cytology, and introduction of LBC.
Malignant Mesothelioma in Body Fluids: with Special Reference to Differential Diagnosis from Metastatic Adenocarcinoma.
Jin Ho Paik, Jin Haeng Chung, Baek Hui Kim, Gheeyoung Choe
Korean J Pathol. 2009;43(5):458-466.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.458
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AbstractAbstract PDF
BACKGROUND
Malignant mesothelioma (MM) is a rare malignant neoplasm occurring in pleura, pericardium, and peritoneum. The differential diagnosis between MM and metastatic adenocarcinoma (MA) causes diagnostic, staging, and therapeutic dilemmas. Herein, we investigated characteristic cytologic features of MM.
METHODS
Cytologic specimens of MM (n=10), MA (n=25), and reactive mesothelial hyperplasia (n=10) were retrieved and reviewed from archival materials in the Department of Pathology, Seoul National University Bundang Hospital from May 2003 to July 2008.
RESULTS
MM showed tumor cell clusters and singly scattered malignant tumor cells forming single cell populations with sparse reactive benign mesothelial cells. In contrast, MA showed distinct two cell populations of tumor cell clusters and scattered reactive mesothelial cells. Furthermore, MM frequently exhibited a characteristic long chain-like arrangement (hand-in-hand appearance) and intercellular windows, which were rarely evident in MA. Variable nuclear size, relatively consistent nuclear-cytoplasmic ratio, bior multi-nucleation, and lacy cytoplasmic borders were also frequently observed in MM.
CONCLUSIONS
Differential diagnosis of MM from MA in body fluids is possible based on meticulous examination of certain cytologic parameters, which could have significant implications in staging and treatment.
Case Reports
Squamous Cell Carcinoma of an Ileal Neobladder: A Case Report.
Ran Hong, Dong Youl Choi, Dae Eun Shin, Hyung Yoon Moon, Keun Hong Kee
Korean J Pathol. 2009;43(5):467-470.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.467
  • 2,548 View
  • 13 Download
AbstractAbstract PDF
Bladder reconstruction using bowel segments, especially the ileum, has become a realistic option for urinary diversion. There is only one prior case of squamous cell carcinoma of the ileal neobladder that has been reported in the clinical literature. Here we report a patient with a spectrum of squamous cell lesions, including squamous cell carcinoma, sarcomatoid carcinoma, squamous papilloma and squamous metaplasia that developed in the ileal neobladder. A 46-year-old woman underwent a hysterectomy, cystectomy and ileocystoplasty for tuberculosis 25 years previously complained of urinary frequency and gross hematuria for one week. A pelvic CT revealed a 6.3 cm mass in the neobladder. The histopathological examination showed an 11x8 cm polypoid fragile mass with a microscopically well-differentiated squamous cell carcinoma, squamous papilloma and non-tumor squamous metaplasia.
Malignant Peripheral Nerve Sheath Tumors of the Bilateral Adrenal Glands: Are They Metachronous Primary Tumors: A Case Report.
Jae Hong Park, Seung Yeon Ha, Hyun Yee Cho
Korean J Pathol. 2009;43(5):471-474.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.471
  • 2,118 View
  • 19 Download
AbstractAbstract PDF
Malignant peripheral nerve sheath tumors (MPNSTs) have rarely been reported to occur in the adrenal gland and all of the reported cases were associated with neurofibromatosis, pheochromocytoma or ganglioneuroma. We present here a case of MPNST in the bilateral adrenal glands without any history of neurofibromatosis or combined tumor. Histologic examination showed the tumor cells had a spindle to ovoid shape, they were arranged in sweeping fascicles and there were frequent mitotic figures. The immunohistochemical and ultrastructural features of the tumor are also presented. To the best of our knowledge, this is the first report in the English medical literature about MPNSTs in the bilateral adrenal glands without any history of neurofibromatosis or combined tumor.
Metastatic Osteosarcoma to the Prostate: A Case Report.
Hyoung Yeon Seo, Jae Hyuk Lee, Chang Soo Park, Jin Gyoon Park, Sung Taek Jung
Korean J Pathol. 2009;43(5):475-477.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.475
  • 3,530 View
  • 22 Download
AbstractAbstract PDF
The most common site for the metastasis of osteosarcoma is the lung, and other sites of metastases include the bone, lymph node, pleura and liver. Although unusual extrapulmonary metastases have been reported with the improvement of the therapeutic results for the primary lesions, they are exceptionally rare. We report here on a case of prostatic metastasis of an osteosarcoma of the proximal tibia, and this developed seven years after successful resection, and four years after resection of a pulmonary metastasis. Radical prostatectomy was performed, and histological examination demonstrated metastatic osteosarcoma. To the best of our knowledge, this is the first case of prostatic metastasis of osteosarcoma in the medical literature.

JPTM : Journal of Pathology and Translational Medicine