Journal of Pathology and Translational Medicine

Review

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee; J Pathol Transl Med. 2024;58(3):103-116. Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15

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Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

Citations

Citations to this article as recorded by

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIG
F. Lordick, M.E. Mauer, G. Stocker, C.A. Cella, I. Ben-Aharon, G. Piessen, L. Wyrwicz, G. Al-Haidari, T. Fleitas-Kanonnikoff, V. Boige, R. Lordick Obermannová, U.M. Martens, C. Gomez-Martin, P. Thuss-Patience, V. Arrazubi, A. Avallone, K.K. Shiu, P. Artru
Annals of Oncology.2025; 36(2): 197. CrossRef
PD-L1 as a Biomarker in Gastric Cancer Immunotherapy
Yunjoo Cho, Soomin Ahn, Kyoung-Mee Kim
Journal of Gastric Cancer.2025; 25(1): 177. CrossRef
PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities
Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J. M. Sullman, Nahid Eskandari
Clinical and Experimental Medicine.2025;[Epub] CrossRef
PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials
V. Formica, C. Morelli, L. Fornaro, S. Riondino, M. Rofei, E. Fontana, E.C. Smyth, M. Roselli, H.-T. Arkenau
ESMO Open.2024; 9(11): 103967. CrossRef

Case Report

A Metastatic Granulocyte Colony-Stimulating Factor Producing Sarcomatoid Carcinoma of the Lung Causing Jejunal Intussusception: Report of a Case.: Min Eui Hong, Soon Auck Hong, Gui Young Kwon, Tae Jin Lee, Eon Sub Park, Sung Jae Cha, Jae Hyuk Do, Jae Hyung Yoo; Korean J Pathol. 2011;45(2):205-208.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.205

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Abstract PDF: A 75-year-old man was referred to our hospital with intestinal obstruction caused by intussusception. Abdominal computed tomography (CT) revealed seven polypoid masses in the small intestine, while chest CT revealed a mass in the right lower lobe. Preoperative laboratory tests showed white blood cell (WBC) and neutrophil differential counts of 63,630/mm3 and 95%, respectively. The serum granulocyte colony-stimulating factor (G-CSF) was 114 pg/mL, which was elevated (normal range, <18.1 pg/mL). After resection of the small bowel, the WBC count decreased to 20,510/mm3. The pathology showed a poorly differentiated carcinoma with sarcomatous components confirmed by positive immunostaining of cytokeratin (AE1/AE3) and vimentin in the small intestine. Furthermore, immunohistochemistry with specific monoclonal antibodies against G-CSF was positive. A lung biopsy revealed the same histological findings as the small intestine lesion. Therefore, the patient was diagnosed as having a G-CSF producing sarcomatoid carcinoma of the lung with metastasis to the small intestine.

Original Articles

Primary Splenic Vascular Lesions: A Clinicopathologic, Immunophenotypic and Radiopathologic Correlation Study of 40 Cases.: Young Wha Koh, Heejin Lee, Gawon Choi, Gui Young Kwon, Eun Ju Kim, Jooryung Huh; Korean J Pathol. 2010;44(5):502-512.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.502

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Abstract PDF

BACKGROUND
Primary splenic vascular lesions include the tumor and the inflammatory condition. A primary splenic vascular tumor is rare but is the most common tumor of the benign primary splenic tumors.
METHODS
We describe the clinicopathological, radiological, and immunophenotypical findings of 40 cases of primary vascular lesions identified at our hospital from 1996 to 2009.
RESULTS
The patients included 18 men and 22 women, aged 12 to 74 years, with a mean of 43.3-years and median of 40-years. They comprised 14 hemangiomas (35%), 13 lymphangiomas (32.5%), three hamartomas (7.5%), three littoral cell angiomas (7.5%), three sclerosing angiomatoid nodular transformations (SANT, 7.5%) and four angiosarcomas (10%). The majority of the patients (65%) were asymptomatic. Some of the patients (32.5%) complained of abdominal pain, and 2.5% of the patients presented with fever. Metastases were identified in 75% of the patients with an angiosarcoma at the initial work-up. One angiosarcoma patient died of the disease despite adjuvant chemoradiotherapy. The radiological findings for hamartoma, littoral cell angioma, and SANT were nonspecific. Microscopically, six types of vascular lesions showed classic morphological and immunophenotypical features of their type.
CONCLUSIONS
One should be aware of rare splenic vascular lesions when radiological findings are nonspecific. Histomorphological and immunophenotypical features are helpful for the differential diagnosis.

Citations

Citations to this article as recorded by

A Case of Splenic Hamartoma Diagnosed by Contrast-enhanced Ultrasonography and Magnetic Resonance Imaging
Hyeon Sik Kim, Tae Hyo Kim, Jae Min Lee, Hyun Jin Kim, Woon Tae Jung, Ok Jae Lee, Ji Eun Kim, Kyung Soo Bae
The Korean Journal of Gastroenterology.2014; 64(6): 380. CrossRef

HER-2/neu Oncogene Amplification by Chromogenic in situ Hybridization and Immunohistochemical Expression of Topoisomerase II-alpha in the Breast Cancer.: Tae Jin Lee, Hyung Goon Oh, Gui Young Kwon, Mi Kyung Kim, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2003;37(1):26-34.

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Abstract PDF: BACKGROUND
Amplifications of the HER-2/neu oncogene and the Topoisomerase II-alpha gene are important determiners of the response to chemotherapy in the breast cancer. For detecting HER-2/neu amplification, fluorescent in situ hybridization and immunohistochemistry are currently regarded as standard methods. Chromogenic in situ hybridization (CISH) is investigated as a new modification of in situ hybridization. The purpose of this study is to compare the efficacy of CISH and immunohistochemistry (IHC) in detecting HER-2/neu oncogene amplification and to investigate the prognostic significance of the HER-2/neu oncogene and the Topoisomerase II-alpha gene in breast cancer.
METHODS
Using CISH and IHC the amplifications and protein expressions of the HER-2/neu oncogene were studied on paraffin sections of 43 infiltrating duct carcinomas. The expression of the Topoisomerase II-alpha gene was studied immunohistochemically.
RESULTS
Of the 43 infiltrating duct carcinomas, amplifications of the HER-2/neu oncogene by CISH were observed in 8 cases (18.6%), and the HER-2/neu protein was deemed overexpressed by IHC in 9 cases (20.9%). The amplifications of the HER-2/neu oncogene showed a statistically significant correlation with tumor size, histological grade, and the Topoisomerase II-alpha index. The Topoisomerase II-alpha index showed a statistically significant correlation with tumor size, lymph node status, stage, histologic grade, and estrogen receptor status.
CONCLUSIONS
CISH is a useful alternative for determining HER-2/neu amplification, especially for confirming the immunohistochemical staining results. HER-2/neu amplification and the Topoisomerase II-alpha gene index may be prognostic factors of breast cancer.

Case Report

Intravascular Leiomyosarcoma of the Femoral Vein: A Case Report.: Soon Auck Hong, Min Eui Hong, Gui Young Kwon, Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2008;42(4):232-235.

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Abstract PDF: Intravascular leiomyosarcomas of the femoral vein are extremely rare. Our patient was initially diagnosed with a deep vein thrombosis based on ultrasonography and venography. The thrombectomy specimen consisted of typical spindle cells with variable anaplasia arranged in a fasciculating and interlacing pattern. The final diagnosis was proved to be an intravascular leiomyosarcoma confirmed by immunohistochemical studies for smooth muscle actin, desmin, vimentin, CD34 and CD68.

Original Articles

Correlation of Expression of galectin-3, skp2, p27 and cyclin D1 in Benign and Malignant Thyroid Lesions.: Soon Auck Hong, Min Eui Hong, Gui Young Kwon, Mi Kyung Kim; Korean J Pathol. 2008;42(3):134-139.

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Abstract PDF: BACKGROUND
The overexpression of cyclin D1 and galectin-3 and the loss of p27 in thyroid cancers have recently been reported by many studies. The S-phase kinase associated protein 2 (skp2) plays an important role in the degradation of p27. We compared the correlation of the expressions of galectin-3, p27, cyclin D1 and skp2 in thyroid lesions.
METHODS
Sixty five cases were included in this study and immunohistochemical staining for galectin-3, skp2, p27 and cyclin D1 was performed.
RESULTS
The expression of galectin-3 increased in the order of nodular hyperplasia, follicular adenoma, follicular carcinoma and papillary carcinoma (p<0.01). The expression rate of skp2 was 0% for nodular hyperplasia, 16.7% for follicular adenoma, 33.3% for follicular carcinoma and 16.7% for papillary carcinoma. The loss of the expression of p27 was more frequently detected in papillary carcinoma as compared with nodular hyperplasia (p<0.01). The increased expression of cyclin D1 was noted in follicular adenoma and carcinoma as compared with nodular hyperplasia (p=0.043). The expression of galectin-3 was related with the loss of a p27 expression (p<0.01), and the expression of skp2 was related with the expression of the cyclin D1 (p=0.022).
CONCLUSIONS
Galectin-3 appears to be the most useful marker for making the diagnosis of thyroid lesions. The loss of a p27 expression can help differentiate nodular hyperplasia and papillary carcinoma, and the determining the expression of cyclin D1 may be helpful for the differential diagnosis of nodular hyperplasia and follicular neoplasm.

Expression of Survivin, HSP90, Bcl-2 and Bax Proteins in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.: Sang Dae Lee, Sung Woong Park, Soon Auck Hong, Gui Young Kwon, Tae Jin Lee; Korean J Pathol. 2006;40(5):333-338.

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Abstract PDF: BACKGROUND
Survivin belongs to the inhibitor of apoptosis family, and it has recently been found to be expressed in most solid tumors. Therefore, its expression is suggested to have prognostic significance. However, no data are available concerning the significance of survivin for the carcinogenesis of bladder cancer.
METHODS
In order to induce urothelial tumor in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was administered to male Sprague-Dawley rats for 30 weeks. We used immunohistochemistry to investigate the expressions of survivin, HSP90, Bcl-2 and Bax in rat bladder carcinogenesis.
RESULTS
Urothelial cell hyperplasia, papilloma, non-invasive urothelial carcinoma and invasive urothelial carcinoma appeared at 5, 10, 20 and 30 weeks, respectively. The expressions of survivin and HSP90 increased sequentially from normal mucosa, hyperplasia, papilloma, non-invasive urothelial carcinoma to invasive urothelial carcinoma. The expressions of Bcl-2 and Bax did not increase, however the number of cases with more than 1 of Bcl-2/Bax expression ratio increased sequentially during the progression of urothelial lesion. The expression of survivin showed a statistically significant correlation with the expression of HSP90 and the Bcl-2/Bax expression ratio.
CONCLUSIONS
Our findings suggest that survivin may be involved in the carcinogenesis of rat bladder and its expression is correlated with the expression of HSP90 and the Bcl-2/Bax expression ratio.

Expression of Cyclins (D1, A, E, and B1) in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.: Gui Young Kwon, Eon Sub Park, Sung Geun Bong, Tae Jin Lee, Mi Kyung Kim, Jae Hyung Yoo, Kye Yong Song; Korean J Pathol. 2003;37(4):255-262.

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Abstract PDF: BACKGROUND
Cell cycle deregulation plays a major role in chemical multistage carcinogenesis.Therefore, the evaluation of cell cycle proteins is important.
METHODS
In order to induce carcinogenesis in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)was administered to male Sprague-Dawley rats for 30 weeks. Expressions of cyclin D1, A, E, and B1 were examined by immunohistochemical stainings.
RESULTS
Urothelial cell hyperplasia appeared at 5 weeks, followed by papilloma at 10 weeks. Superficial carcinoma was observed at 20 weeks, and invasive carcinoma developed in 40% (4/10) of the rats at 30 weeks. Expressions of cyclin D1 and A increased sequentially from normal mucosa throughhyperplasia, papilloma, and carcinoma (p<0.01). Expressions of cyclin D1, B1 and cyclin Ewere higher in invasive carcinomas than in superficial carcinomas (p<0.01). In contrast, therewas no significant difference in the expression of cyclin B1 between hyperplasia, papillomaand superficial carcinoma.
CONCLUSIONS
The present results indicate the important roles of cyclin D1 and A in the development of BBN-induced urothelial carcinoma of rats. Aberrantexpression of cyclin B1 and E may contribute to the progression from superficial to invasivebladder cancer rather than tumorigenesis.

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