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Basaloid Squamous Cell Carcinoma of the Head and Neck: Subclassification into Basal, Ductal, and Mixed Subtypes Based on Comparison of Clinico-pathologic Features and Expression of p53, Cyclin D1, Epidermal Growth Factor Receptor, p16, and Human Papillomavirus
Kyung-Ja Cho, Se Un Jeong, Sung Bae Kim, Sang-wook Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
J Pathol Transl Med. 2017;51(4):374-380.   Published online June 8, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.03
  • 13,747 View
  • 379 Download
  • 9 Web of Science
  • 11 Crossref
AbstractAbstract PDF
Background
Basaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma with distinct pathologic characteristics. The histogenesis of BSCC is not fully understood, and the cancer has been suggested to originate from a totipotent primitive cell in the basal cell layer of the surface epithelium or in the proximal duct of secretory glands.
Methods
Twenty-six cases of head and neck BSCC from Asan Medical Center, Seoul, Korea, reported during a 14-year-period were subclassified into basal, ductal, and mixed subtypes according to the expression of basal (cytokeratin [CK] 5/6, p63) or ductal markers (CK7, CK8/18). The cases were also subject to immunohistochemical study for CK19, p53, cyclin D1, epidermal growth factor receptor (EGFR), and p16 and to in situ hybridization for human papillomavirus (HPV), and the results were clinico-pathologically compared.
Results
Mixed subtype (12 cases) was the most common, and these cases showed hypopharyngeal predilection, older age, and higher expression of CK19, p53, and EGFR than other subtypes. The basal subtype (nine cases) showed frequent comedo-necrosis and high expression of cyclin D1. The ductal subtype (five cases) showed the lowest expression of p53, cyclin D1, and EGFR. A small number of p16- and/or HPV-positive cases were not restricted to one subtype. BSCC was the cause of death in 19 patients, and the average follow-up period for all patients was 79.5 months. Overall survival among the three subtypes was not significantly different.
Conclusions
The results of this study suggest a heterogeneous pathogenesis of head and neck BSCC. Each subtype showed variable histology and immunoprofiles, although the clinical implication of heterogeneity was not determined in this study.

Citations

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The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence
Jee Soon Kim, Youn Soo Lee, Min Jung Jung, Yong Kil Hong
J Pathol Transl Med. 2016;50(6):419-425.   Published online October 6, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.30
  • 7,433 View
  • 228 Download
  • 17 Web of Science
  • 17 Crossref
AbstractAbstract PDF
Background
The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.
Methods
One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.
Results
Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).
Conclusions
Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

Citations

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The Role of TWIST in Ovarian Epithelial Cancers
Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi
Korean J Pathol. 2014;48(4):283-291.   Published online August 26, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.283
  • 7,058 View
  • 39 Download
  • 11 Crossref
AbstractAbstract PDF
Background

Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.

Methods

We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.

Results

The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.

Conclusions

Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

Citations

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  • E-Cadherin Expression in Relation to Clinicopathological Parameters and Survival of Patients with Epithelial Ovarian Cancer
    Michal Kielbik, Izabela Szulc-Kielbik, Magdalena Klink
    International Journal of Molecular Sciences.2022; 23(22): 14383.     CrossRef
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IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma
Ji Young Park, Misun Choe, Yuna Kang, Sang Sook Lee
Korean J Pathol. 2014;48(2):108-116.   Published online April 28, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.108
  • 6,937 View
  • 32 Download
  • 4 Crossref
AbstractAbstract PDF
Background

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes.

Methods

We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed.

Results

Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival.

Conclusions

IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.

Citations

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  • IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas
    Natividad Martin-Morales, Miguel Padial-Molina, Isabel Tovar, Virginea De Araujo Farias, Pedro Hernández-Cortés, Esperanza Ramirez-Moreno, Mercedes Caba-Molina, Justin Davis, Alejandro Carrero Castaño, Jose Mariano Ruiz de Almodovar, Pablo Galindo-Moreno,
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    Shuping You, Yun Guan, Weihong Li
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Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia
Tae Eun Kim, Hwal Woong Kim, Kyung Eun Lee
Korean J Pathol. 2014;48(1):24-29.   Published online February 25, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.24
  • 8,260 View
  • 42 Download
  • 4 Crossref
AbstractAbstract PDF
Background

This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections.

Methods

A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry.

Results

HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively.

Conclusions

This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes.

Citations

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  • Screening for High-Risk Human Papillomavirus Reveals HPV52 and HPV58 among Pediatric and Adult Patient Saliva Samples
    Hunter Hinton, Lorena Herrera, Sofia Valenzuela, Katherine M. Howard, Karl Kingsley
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    群欢 黄
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    Youn Jin Choi, Eun Young Ki, Chuqing Zhang, Wendy C. S. Ho, Sung-Jong Lee, Min Jin Jeong, Paul K. S. Chan, Jong Sup Park, Xuefeng Liu
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Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis
Miji Lee, Sung Bae Kim, Sang-wook Lee, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho
Korean J Pathol. 2013;47(2):148-157.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.148
  • 6,886 View
  • 48 Download
  • 5 Crossref
AbstractAbstract PDF
Background

Human papillomavirus (HPV)-related tonsillar squamous cell carcinoma (TSCC) has recently been characterized as a distinct subset with a favorable prognosis. The prevalence and clinicopathologic significance of HPV-related TSCC in Koreans are not well known.

Methods

HPV in situ hybridization (ISH) accompanied by p53, p16, pRb, and cyclin D1 immunohistochemical staining were performed on 89 resection cases of TSCC from 2000 through 2010.

Results

HPV was detected by ISH in 59 of 89 cases (66.3%). HPV-positive TSCCs were more common in younger ages (p=0.005), and tumor sizes were smaller in the HPV-positive compared to the HPV-negative group (p=0.040). Positive HPV staining was significantly correlated with p16 expression (p<0.001), pRb inactivation (p=0.003), and cyclin D1 down-regulation (p<0.001) but not with p53 expression (p=0.334). Seventeen cases that showed p16-immunopositivity with HPV-negativity by ISH were retested by HPV typing; HPV DNA was not detected in all cases. There was no significant difference between HPV-positive and HPV-negative patients either in the disease-specific survival (DSS, p=0.857) or overall survival (p=0.910). Furthermore, pRb-inactivated cases showed better DSS (p=0.023), and p53-positive cases showed worse DSS (p=0.001).

Conclusions

Although high HPV prevalence was noted, it was not correlated with histopathologic findings or survival benefit. In addition to p53 expression, pRb inactivation along with p16 overexpression and down-regulation of cyclin D1 are thought to be important pathogenetic steps for developing TSCCs.

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  • Assessment of the Mutation Profile of Tonsillar Squamous Cell Carcinomas Using Targeted Next-Generation Sequencing
    Ha Young Park, Joong Seob Lee, Jee Hye Wee, Jeong Wook Kang, Eun Soo Kim, Taeryool Koo, Hee Sung Hwang, Hyo Jung Kim, Ho Suk Kang, Hyun Lim, Nan Young Kim, Eun Sook Nam, Seong Jin Cho, Mi Jung Kwon
    Biomedicines.2023; 11(3): 851.     CrossRef
  • Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea
    Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho
    Journal of Pathology and Translational Medicine.2023; 57(3): 166.     CrossRef
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    Hyunchul Kim, Mi Jung Kwon, Bumjung Park, Hyo Geun Choi, Eun Sook Nam, Seong Jin Cho, Kyueng-Whan Min, Eun Soo Kim, Hee Sung Hwang, Mineui Hong, Taeryool Koo, Hyo Jung Kim
    Indian Journal of Surgical Oncology.2021; 12(S1): 134.     CrossRef
  • Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas
    Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
    Journal of Pathology and Translational Medicine.2020; 54(5): 411.     CrossRef
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    Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
    Human Pathology.2014; 45(7): 1327.     CrossRef
Expression of CHOP in Squamous Tumor of the Uterine Cervix
Hyun Hee Chu, Jun Sang Bae, Kyoung Min Kim, Ho Sung Park, Dong Hyu Cho, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung
Korean J Pathol. 2012;46(5):463-469.   Published online October 25, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.463
  • 7,408 View
  • 38 Download
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AbstractAbstract PDF
Background

High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53.

Methods

Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I).

Results

CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively).

Conclusions

Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.

Citations

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Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression.
Nari Shin, Hye Yeon Kim, Woo Kyung Kim, Min Gyung Park, Kyung Bin Kim, Dong Hoon Shin, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Gi Young Huh, Mee Young Sol, Do Youn Park
Korean J Pathol. 2011;45(1):69-78.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.69
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AbstractAbstract PDF
BACKGROUND
It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer.
METHODS
We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH).
RESULTS
Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes.
CONCLUSIONS
Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type.

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    Archives of Pathology & Laboratory Medicine.2013; 137(8): 1047.     CrossRef
  • Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes
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Uncoupling Protein 2 (UCP2) and p53 Expression in Invasive Ductal Carcinoma of Breast.
Kyu Yeoun Won, Gou Young Kim, Youn Wha Kim, Sung Jig Lim, Jeong Yoon Song
Korean J Pathol. 2010;44(6):565-570.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.565
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AbstractAbstract PDF
BACKGROUND
Uncoupling protein 2 (UCP2) is a recently identified mitochondrial inner membrane anion carrier and a negative regulator of reactive oxygen species production. In this study, we evaluated the characteristics and relationships of UCP2 and p53 expression in breast cancer tissues.
METHODS
Tissue microarray slides from 107 cases of invasive ductal carcinoma of the breast were constructed, UCP2 and p53 immunohistochemical staining was conducted, and clinicopathological correlations were investigated.
RESULTS
UCP2 expression in invasive ductal carcinoma was high in 53 cases (49.5%), while p53 expression in invasive ductal carcinoma was high in 37 cases (34.6%). UCP2 expression was correlated significantly with histological grade (p = 0.038) and mitotic count (p = 0.050). UCP2 expression was correlated significantly with p53 expression in invasive ductal carcinoma of the breast (p = 0.045). UCP2 expression (p = 0.8308) and p53 expression (p = 0.3292) showed no significant difference for the overall survival rate in patients with invasive ductal carcinoma.
CONCLUSIONS
UCP2 expression in invasive ductal carcinoma increased proportionally with histological grade and mitotic count. High UCP2 expression in invasive ductal carcinoma was observed in conjunction with high p53 expression.

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The Expressions of E2F1 and p53 in Gastrointestinal Stromal Tumors and Their Prognostic Significance.
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jong Seok Lee, Chan Heun Park, Woon Geon Shin
Korean J Pathol. 2009;43(3):212-220.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.212
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AbstractAbstract PDF
BACKGROUND
E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors.
METHODS
Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate.
RESULTS
1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008).
CONCLUSIONS
E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.

Citations

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  • Comparison of tissue microarray and full section in immunohistochemistry of gastrointestinal stromal tumors
    Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jun Ho Park, Chan Heun Park, Won Jae Lee
    Pathology International.2009; 59(12): 851.     CrossRef
Expression of the GLUT1 and p53 Protein in Atypical Mucosal Lesions Obtained from Gastric Biopsy Specimens.
In Gu Do, Youn Wha Kim, Yong Koo Park
Korean J Pathol. 2006;40(1):32-38.
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AbstractAbstract PDF
BACKGROUND
The diagnosis of atypical mucosal lesions by performing hematoxylin-eosin staining is too subjective, and it is also subject to considerable inter-observer variation. There is a need for reliable immunohistochemical markers that can give reproducible results and that are not subject to individual interpretation.
METHODS
We reviewed a total of 199 cases of gastric biopsy specimens, which were all diagnosed as atypical mucosal lesions, and 124 cases of the adenocarcinomas specimens had been classified from category 1 (C1) to C5 according to the Vienna classification. We also examined the immunohistochemical expressions of the glucose transporter GLUT1 and the p53 protein in the gastric biopsy specimens to determine if they were useful markers for differentiatial diagnosis under the Vienna classifications.
RESULTS
None of the specimens in categories C1 to C3 showed GLUT1 expression, but 10.1% of the C4 specimens and 25.0% of the C5 specimens were GLUT1-positive (p<0.05). The expression of p53 was undetectable in the C1 specimens, but this was expressed in 2.9% of the C2 specimens, 15.6% of the C3 specimens, 37.8% of the C4 specimens, and 65.3% of the C5 specimens (p<0.05).
CONCLUSIONS
The Vienna classification is very applicable to the gastric biopsy specimens of the atypical mucosal lesions, and the GLUT1 and p53 expressions are candidates as highly useful markers to differentiate the Vienna C4 lesions from the C3 and C5 lesions.

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