Journal of Pathology and Translational Medicine

Original Articles

Morphometric Analysis of Thyroid Follicular Cells with Atypia of Undetermined Significance: Youngjin Kang, Yoo Jin Lee, Jiyoon Jung, Youngseok Lee, Nam Hee Won, Yang Seok Chae; J Pathol Transl Med. 2016;50(4):287-293. Published online June 13, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.04

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Background
Atypia of undetermined significance (AUS) is a category that encompasses a heterogeneous group of thyroid aspiration cytology. It has been reclassified into two subgroups based on the cytomorphologic features: AUS with cytologic atypia and AUS with architectural atypia. The nuclear characteristics of AUS with cytologic atypia need to be clarified by comparing to those observed in Hashimoto thyroiditis and benign follicular lesions.
Methods
We selected 84 cases of AUS with histologic follow-up, 24 cases of Hashimoto thyroiditis, and 26 cases of benign follicular lesions. We also subcategorized the AUS group according to the follow-up biopsy results into a papillary carcinoma group and a nodular hyperplasia group. The differences in morphometric parameters, including the nuclear areas and perimeters, were compared between these groups.
Results
The AUS group had significantly smaller nuclear areas than the Hashimoto thyroiditis group, but the nuclear perimeters were not statistically different. The AUS group also had significantly smaller nuclear areas than the benign follicular lesion group; however, the AUS group had significantly longer nuclear perimeters. The nuclear areas in the papillary carcinoma group were significantly smaller than those in the nodular hyperplasia group; however, the nuclear perimeters were not statistically different.
Conclusions
We found the AUS group to be a heterogeneous entity, including histologic follow-up diagnoses of papillary carcinoma and nodular hyperplasia. The AUS group showed significantly greater nuclear irregularities than the other two groups. Utilizing these features, nuclear morphometry could lead to improvements in the accuracy of the subjective diagnoses made with thyroid aspiration cytology.

Citations

Citations to this article as recorded by

Meta-analysis on the utility of morphometry in the cytological differential diagnosis of thyroid neoplasms
Prema Saldanha
MGM Journal of Medical Sciences.2024; 11(1): 49. CrossRef
Morphometric study in thyroid tumors
Iuliana Mohorea, Bogdan Socea, Alexandru Carâp, Dragoș Șerban, Zenaida Ceaușu, Mihail Ceaușu
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef
The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology
Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong
Journal of Pathology and Translational Medicine.2018; 52(6): 404. CrossRef

Clinicopathological Analysis of Hepatocellular Adenoma According to New Bordeaux Classification: Report of Eight Korean Cases: Hyunchul Kim, Ja-June Jang, Dong-Sik Kim, Beom Woo Yeom, Nam Hee Won; Korean J Pathol. 2013;47(5):411-417. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.411

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Abstract PDF

Background

Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. A subtype classification of HCA (hepatocyte nuclear factor 1α [HNF1α]-mutated, β-catenin-mutated HCA, inflammatory HCA, and unclassified HCA) has recently been established based on a single institutional review of a HCA series by the Bordeaux group.

Methods

We used histologic and immunohistochemical parameters to classify and evaluate eight cases from our institution. We evaluated the new classification method and analyzed correlations between our results and those of other reports.

Results

Seven of our eight cases showed histologic and immunohistochemical results consistent with previous reports. However, one case showed overlapping histologic features, as previously described by the Bordeaux group. Four cases showed glutamine synthetase immunohistochemical staining inconsistent with their classification, indicating that glutamine synthetase staining may not be diagnostic for β-catenin-mutated HCA. HNF1α-mutated HCA may be indicated by the absence of liver fatty acid binding protein expression. Detection of amyloid A may indicate inflammatory HCA. HCA with no mutation in the HNF1α or β-catenin genes and no inflammatory protein expression is categorized as unclassified HCA.

Conclusions

Although the new classification is now generally accepted, validation through follow-up studies is necessary.

Citations

Citations to this article as recorded by

Relevance of morphological features for hepatocellular adenoma classification in pathology practice
Carla Henriques Agostini, Osmar Damasceno Ribeiro, Arlete Fernandes, Adriana Caroli-Bottino, Vera Lucia Pannain
Surgical and Experimental Pathology.2020;[Epub] CrossRef
The molecular functions of hepatocyte nuclear factors – In and beyond the liver
Hwee Hui Lau, Natasha Hui Jin Ng, Larry Sai Weng Loo, Joanita Binte Jasmen, Adrian Kee Keong Teo
Journal of Hepatology.2018; 68(5): 1033. CrossRef
Hepatocellular adenoma: Classification, variants and clinical relevance
Paulette Bioulac-Sage, Christine Sempoux, Charles Balabaud
Seminars in Diagnostic Pathology.2017; 34(2): 112. CrossRef
A Limited Immunohistochemical Panel Can Subtype Hepatocellular Adenomas for Routine Practice
Brent K. Larson, Maha Guindi
American Journal of Clinical Pathology.2017; 147(6): 557. CrossRef
Hepatocellular Neoplasms Arising in Association With Androgen Use
Sounak Gupta, Bita V. Naini, Richard Munoz, Rondell P. Graham, Benjamin R. Kipp, Michael S. Torbenson, Taofic Mounajjed
American Journal of Surgical Pathology.2016; 40(4): 454. CrossRef
Pigmented hepatocellular adenomas have a high risk of atypia and malignancy
Taofic Mounajjed, Saba Yasir, Patrice A Aleff, Michael S Torbenson
Modern Pathology.2015; 28(9): 1265. CrossRef

Effect of Selective Cyclooxygenase 2 Inhibitor in TCDD Pre-exposed Thyroid Papillary Carcinoma Cell Line.: Hae Sung Kim, Kwang Sung Ahn, Jeong Hyeon Lee, Yang Seok Chae, Nam Hee Won, Jong Sang Choi, Chul Hwan Kim; Korean J Pathol. 2011;45(1):1-8.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.1

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Abstract PDF

BACKGROUND
Cyclooxygenase 2 (COX-2) is related to carcinogenesis and progression of cancer. COX-2 has been detected in thyroid cancer. This suggests that COX-2 inhibitor may be useful to control the growth of thyroid cancer cells as well as the progression of thyroid cancer. Tetrachlorodibenzodioxin (TCDD), acting as an inflammatory cytokine, directly induces the expression of COX-2. We examine whether TCDD controls the effect of COX-2 inhibitor on thyroid cancer cells.
METHODS
The effects of TCDD and celecoxib on thyroid papillary carcinoma cell line (SNU790) were examined using cell proliferation and fluorescence-activated cell sorting analysis. Western blot analysis was performed to determine the expressed COX-2 levels and the cell cycle-related proteins. The matrix metalloproteinase-2 (MMP-2) expression and gelatinolytic activity were examined using real time-polymerase chain reaction and zymography.
RESULTS
TCDD directly induced the growth of SNU790 and the expression of cyclin D1, cyclin A, cyclin E, p21 and COX-2. Celecoxib suppressed the growth of SNU790 and the expression of cyclin D1 and cyclin E. Celecoxib reduced the MMP-2 expression and the gelatinolytic activity, but those effects were decreased in the SNU790 by either pre-treatment with TCDD or co-treatment with TCDD and celecoxib.
CONCLUSIONS
Celocoxib effect is directly reduced depending on the exposure to TCDD. TCDD exposure should be considered in the treatment with Celecoxib.

Citations

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Histone H3 phosphorylation, immediate-early gene expression, and the nucleosomal response: a historical perspective1This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.
Shannon Healy, Protiti Khan, Shihua He, James R. Davie
Biochemistry and Cell Biology.2012; 90(1): 39. CrossRef

Practical Standardization in Renal Biopsy Reporting.: So Young Jin, Hyeon Joo Jeong, Sun Hee Sung, Beom Jin Lim, Jee Young Han, Soon Won Hong, Hyun Ee Yim, Yeong Jin Choi, Yong Mee Cho, Myoung Jae Kang, Kyung Chul Moon, Hee Jeong Cha, Seung Yeon Ha, Mi Seon Kang, Mee Young So, Kwang Sun Suh, Jong Eun Joo, Yong Jin Kim, Nam Hee Won, Moon Hyang Park; Korean J Pathol. 2010;44(6):613-622.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.613

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Abstract PDF

BACKGROUND
To standardize renal biopsy reporting and diagnosis, The Renal Pathology Study Group of the Korean Society of Pathologists (RPSKSP) has developed a renal pathology reporting format for the native and allograft kidney.
METHODS
A consensus checklist of a provisional renal biopsy format was sent to all members of the RPSKSP. Feed back opinions regarding the practical application of the checklist to the diagnostic work were received.
RESULTS
Kidney biopsies require three essential examinations: by light microscopy, immunofluorescence (IF), and electron microscopy (EM). A final report of a renal biopsy should include information on specimen adequacy and a description of the morphologic change using a systematic semiquantitative method for each of the compartments, with optional separate IF and EM reports.
CONCLUSIONS
A standard renal biopsy report format is important in establishing clinicopathologic correlations, making reliable prognostic considerations, comparing the findings in sequential biopsies and evaluating the effects of therapy.

Citations

Citations to this article as recorded by

Additional antihypertensive effect of magnesium supplementation with an angiotensin II receptor blocker in hypomagnesemic rats
Kyubok Jin, Tae Hee Kim, Yeong Hoon Kim, Yang Wook Kim
The Korean Journal of Internal Medicine.2013; 28(2): 197. CrossRef
Clinicopathologic Features of IgA-Dominant Postinfectious Glomerulonephritis
Tai Yeon Koo, Gheun-Ho Kim, Hyang Park
Korean Journal of Pathology.2012; 46(2): 105. CrossRef

Case Reports

Hepatoid Thymic Carcinoma: A Case Report.: Jeong Hyeon Lee, Hyunchul Kim, Yang Seok Chae, Nam Hee Won, Jong Sang Choi, Chul Hwan Kim; Korean J Pathol. 2009;43(6):562-565.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.562

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Abstract PDF: We report here on a rare case of hepatoid thymic carcinoma in a 34-year-old man. The patient complained of a high fever and headache, and a 6.6cm-sized anterior mediastinal mass was found on chest computed tomography (CT). There was no hepatic mass seen on abdominal CT. The resected mass consisted of epithelioid cells with abundant eosinophilic cytoplasm, pleomorphic vesicular nuclei and prominent nucleoli, and the mass was surrounded by thymic tissue. The tumor cells were immunopositive for cytokeratin 7, alpha-1-antitrypsin, hepatocyte staining, and epithelial membrane antigen, but they were negative for CD5, alpha-fetoprotein (AFP) and placental alkaline phosphatase, and this all led to a diagnosis of hepatoid thymic carcinoma rather than hepatoid yolk sac tumor. This entity should be included in the differential diagnosis of epithelioid thymic tumors.

Large-Cell Acanthoma: A case report.: Yu Hoon Kim, Seong Jin Cho, Ae ree Kim, Nam Hee Won, Kye Yong Song; Korean J Pathol. 1996;30(2):161-163.

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Abstract PDF: Large-cell acanthoma is a generally hyperkeratotic, sharply demarcated patch on sun-exposed skin with the outstanding pathologic feature being composed of large, relatively uniform keratinocytes. We describe a case of large-cell acanthoma that involved the skin of the nasal bridge. Patient was a 56-year-old women with a tannish brown patch, 2 cm in size and of 5 years' duration. Controversial issues about nosologic entity of large cell acanthoma are discussed.

Original Articles

The p53 Mutation and DNA Ploidy in Human Metastatic Breast Cancer.: Seong Jin Cho, Ae Ree Kim, Nam Hee Won; Korean J Pathol. 1997;31(2):135-144.

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Abstract PDF: The p53 gene, one of the tumor suppressor genes, is believed to play an important role through mutation and overexpression in the progression of various human malignant tumors. To compare the p53 mutation status between the primary and metastatic lesions of breast cancers and to investigate the mutational pattern of p53, immunohistochemistry (IHC) and polymerase chain reaction and single strand conformational polymorphism (PCR-SSCP) were performed in 25 cases of breast cancers with paraffin embedded tissue. Mutant protein products or point mutation were detected through IHC or PCR-SSCP method. And flow cytometrical (FCM) analysis were performed in the same paraffin blocks to correlate the DNA ploidy and p53 mutation. The following results are summarized. 1. The detection of the p53 gene mutation and overexpression of the p53 protein were measured in 40% and 48%, respectively, in 25 primary tumors, either or both methods was detected in 64%. 2. A concordance rate of the p53 protein expression between the primary and metastatic lesions of 25 breast cancers was 100%, but the concordance rate of the p53 gene mutation was 72%. 3. The correlation between the p53 mutation and the DNA aneuploidy was not statistically significant (p=0.38) 4. A p53 mutation by IHC or PCR-SSCP was more frequently detected in grade III breast cancers than in grade I or II. 5. Among 5 to 9 exons of the p53 gene, exon 7 was the most frequent mutation spot in this study. 6. Additional mutation of the p53 gene was developed in the three metastatic lesions. With the above results it is suggested that the p53 protein overexpression by immunohistochemistry is not correlated with the p53 mutation by PCR-SSCP. The p53 mutation pattern between the primary and metastatic lesions are not idenitical and an additional point mutation can occur in the metastatic lesion. The DNA aneuploidy is more frequently detected in the cases with the p53 protein overexpression than in the p53 protein negative, but it is not statistically significant.

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

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Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Case Report

Inflammatory Pseudotumor of the Kidney.: Hwa Eun Oh, Jeong Seok Moon, Sung Jin Cho, Nam Hee Won; Korean J Pathol. 1997;31(6):592-594.

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Abstract PDF: Inflammatory pseudotumor, originally described in the lung, is a relatively rare tumor-like lesion that occurs in various organs and tissues. It is usually well demarcated from the surrounding tissue, however it can be unfortunately resected as a malignant tumor. A few inflammtory pseudotumor in the kidney have been reported in English literature, but there have been no reports in Korea. We report a case with inflammatory pseudotumor of the kidney. A 48 year old woman had an intermittent flank pain on the right side. An ultrasonographic study suggested a renal cell carcinoma and a nephrectomy was done. Grossly, there were two separate masses with a well demarcated yellowish appearance, measuring 2.3 cm and 1.3 cm in diameter, respectively. Histologically, they were composed of smooth muscle actin positive spindle cells and a large number of foamy histiocytes, lymphocytes, and plasma cells in the fibrotic backgound.

Original Article

p53 Mutation and Expression of Rb Protein in Germ Cell Tumors.: Ju Han Lee, Mee Yon Cho, Hae Hyeog Lee, Bom Woo Yeom, Nam Hee Won; Korean J Pathol. 1998;32(12):1074-1080.

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Abstract: We investigated the role of the tumor suppressor genes in the germ cell tumor. Immunohistochemistry (IHC) and polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) for p53 mutation were done in 46 cases of the germ cell tumor with paraffin embedded tissue. The immunohistochemical staining for Rb protein was also performed in the same specimens. The following results were obtained. The overexpression of the p53 protein was detected in 7 of 46 cases (15%). p53 mutation by PCR-SSCP was detected in 1 of 46 cases (2.2%). Expression of Rb protein was negative in 19 cases (41%). These results suggest that p53 mutation does not play an important role in the initiation and progression of germ cell tumors.

Case Reports

Spontaneous Pneumothorax as a Complication of Pulmonary Metastasis of Osteosarcoma A case report.: Min Kyung Kim, Bong Kyung Shin, Wha Eun Oh, Ae Ree Kim, Nam Hee Won, Jong Sang Choi; Korean J Pathol. 1999;33(4):281-284.

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Abstract PDF: Spontaneous pneumothorax is a known, but relatively rare complication of pulmonary metastases of sarcoma. A 19-year-old man was presented with chest pain and dyspnea for three days and was diagnosed as left pneumothorax. After bleb resection, microscopic examination revealed metastatic osteosarcoma forming subpleural fistula and dystrophic calcification. Four years ago, he had had limb salvage operation and chemotherapy for osteosarcoma of left femur. After two and a half years he had a bleb resection for right pneumothorax without any evidence of metastasis. Six months later, he was found to have a 4x3cm sized lung mass in the right lower lobe. After lobectomy, he was diagnosed as pulmonary metastasis of osteosarcoma. Pneumothorax is the common complication of metastatic osteosarcoma to the lung and it may be presented before the pulmonary metastasis is clinically evident. It is important to recognize a pneumothorax of the patients with osteosarcoma as a possible sign of metastases.

Leiomyosarcoma of the Pancreas: A case report.: Bong Kyung Shin, Jung Suk Moon, Hwa Eun Oh, Nam Hee Won, Jong Sang Choi; Korean J Pathol. 1999;33(9):733-736.

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Abstract PDF: Most of the malignant tumors of the pancreas are adenocarcinomas arising from the ductal epithelium. Primary leiomyosarcoma of the pancreas, even though it is the most common sarcoma of the pancreas, is very rare. We present a case of leiomyosarcoma of the pancreas, probably primary, with metastases to the stomach, lymph nodes, and abdominal wall. A 52-year-old woman visited the hospital with vague right upper abdominal pain and weigh loss of 6 kg for 2 months. The radiological and endoscopic examination revealed that she had a large heterogeneous mass, 11 cm in size, in the pancreatic body and tail, a 4 cm-sized mass in the paraaortic area, and a 3 cm-sized polypoid mass in the stomach. Histologically, they were all similar to one another and composed of markedly pleomorphic cells. Immunohistochemical and electron microscopic studies showed definite smooth muscle differentiation of the tumor cells. Two months later, the patient underwent an excision of a new 3 cm mass in the right lower abdominal wall, showing features of well differentiated leiomyosarcoma.

Original Articles

Immunohistochemical Analysis of Transforming Growth Factor (TGF)-beta1 and TGF-beta Receptor II and Quantitative Analysis of TGF-beta1 mRNA during Multistep Hepatocarcinogenesis Induced by Diethylnitrosamine in Sprague-Dawley Rats.: Mee Yon Cho, Ju Han Lee, Yong Koo Kang, Nam Hee Won; Korean J Pathol. 1999;33(11):1009-1023.

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Abstract PDF: Transforming growth factor (TGF)-beta1 plays an important role in hepatocarcinogenesis and has been described as a useful tumor marker and one of the poor prognostic indicators in patients with hepatocellular carcinoma (HCC). To investigate the role and cellular localization of TGF-beta1 during multistep hepatocarcinogenesis we performed a quantitative analysis of TGF-beta1 mRNA and immunohistochemical expression of TGF-beta1 and TGF-beta receptor II (TGF-betarII) in female Sprague-Dawley rats. The experimental groups included neoplastic lesions produced by Solt-Farber's protocol, regenerating liver after partial hepatectomy, and normal control. Quantitative change of TGF-beta1 mRNA was analysed by competitive reverse-transcription polymerase chain reaction (RT-PCR). TGF-beta1 protein and TGF-betarII expression were evaluated by immunohistochemical stain. The discrete tumor nodules were detected on 14th day and then increased in number and size. Three HCCs were induced on 8th or 9th month. RT-PCR demonstrated TGF-beta1 mRNA band in all examples of the normal and regenerating liver, nodules and HCCs. Competitive RT-PCR displayed higher TGF-beta1 mRNA in nodules, HCCs and regenerating liver than in normal controls. Hepatocytes from control and regenerating livers showed weak immunoreactivity for TGF-beta1. In contrast, the cytoplasm of hepatocytes of nodules in 7th, 8th and 9th month and HCCs were intensely stained for TGF-beta1. Some sinusoidal cells showed immunoreactivity for TGF-beta1 in all experimental groups. In early phase of carcinogenesis, the cytoplasm of hepatocytes in liver of 12h, 1d and 3d showed transiently increased immunoreactivity for TGF-beta1 and The immunoreactivity decreased thereafter. TGF-beta1 mRNA was also detected in the neoplastic hepatocytes by in-situ hybridization. Although TGF-betarII expression was correlated with TGF-beta1 immunoreactivity during early phase of carcinogenesis, hepatocytes in most nodules in 7th, 8th, 9th month and carcinomas showed decreased or little immunoreactivity for TGF-betarII. Based on the above results, it is concluded that TGF-beta1 expression increases not only in precancerous nodules but also in HCCs and its increase seems to be correlated with decrease or loss of TGF-betarII expression although its mechanism remains unclear. Hepatocytes may be a major cellular source of TGF-beta1 during hepatocarcinogenesis.

E-Cadherin Expression in Renal Cell Carcinoma according to the Mainz Classification.: Ju Han Lee, Hyun Deuk Cho, Dale Lee, Nam Hee Won; Korean J Pathol. 1999;33(12):1131-1138.

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Abstract PDF: According to the Mainz classification, renal cell carcinoma (RCC) consists of three subtypes: each has characteristic genetic alterations within the chromosomal or mitochondrial DNA. The three subtypes are: clear cell type, chromophil type, and chromophobe type. E-cadherin is a Ca++-dependent adhesion molecule which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. In a normal kidney, E-cadherin is expressed in the distal tubule and the collecting duct, but not in the proximal tubule. We reclassified 110 cases of RCC according to mainz classification. Immunohistochemical staining for E-cadherin was done on twenty eight cases of RCC, including 18 cases of clear cell type, four cases of chromophil type, and six cases of chromophobe type. The results were as follows: 1) of the 110 cases of RCC, 96 cases (87.3%) were of clear cell type, four cases (3.6%) of chromophil type, and ten cases (9.1%) of chromophobe type, 2) there was no significant correlation between the nuclear grade and clinical stage according to each subtype, 3) E-cadherin expression showed a strong positive reaction along the cell membranes in all six cases of chromophobe type. The differential expression of E-cadherin in RCC may suggest that the chromophobe type may have different biologic characteristics from other types of RCC.

K-ras Gene Mutations and Expression of K-ras, p16, Cyclin D1 and p53 in Synchronous Lesions of The Colon Adenoma-Carcinoma Sequences.: Hwa Eun Oh, Seong Jin Cho, Nam Hee Won, Dale Lee, Insun Kim, Bom Woo Yeom; Korean J Pathol. 2001;35(4):291-298.

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Abstract PDF: BACKGROUND
The colorectal adenoma-carcinoma sequence represents a well-known para-digm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma-carcinoma sequence has been well investigated, the studies about tumors of different dignity co-existent in the same patient are rare. K-ras mutation is an early genetic change in colon cancer. The genes involved in the cell cycle such as cyclin D1, p16, and p53 are important in the tumorigenesis of the colon. The aims of this study were to determine K-ras gene mutation and expression of K-ras, p16, cyclin D1 and p53 in synchronous lesions of the colon adenoma-carcinoma sequences and their possible relationship with K-ras mutation.
METHODS
The materials included 45 colonic adenocarcinomas which were accompanied by adenoma (22 low grade and 26 high grade). By using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), we detected K-ras mutation of codon 12. An aberrant K-ras, p16, cyclin D1 and p53 expressions were stained using an immunohistochemical method. RESULTS: K-ras mutation was 52.4% (11/21) of high grade adenomas. K-ras expression was 65.4% (17/26) of high grade adenomas. p16 and cyclin D1 expressions were 50% (11/22) and 90.9% (20/22) of low grade adenomas, respectively. p53 expression was 75.6% (34/45) of adenocarcinomas. There were statistical correlations among K-ras, p16 and cyclin D1.
CONCLUSIONS
These results indicate that the ras gene mutation is an early event and the overexpressions of p16, cyclin D1 and p53 are associated with K-ras mutation and expression in adenoma-carcinoma sequences.

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