Journal of Pathology and Translational Medicine

Review

Tumor immune response and immunotherapy in gastric cancer: Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee; J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.08

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Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.

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Original Articles

Update on the Proposal for Creating a Guideline for Cancer Registration of the Gastrointestinal Tumors (I-2): Eun Sun Jung, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Won Ae Lee, Hee Eun Lee, Sunhoo Park, Jin Hee Sohn, So-Young Jin; Korean J Pathol. 2012;46(5):443-453. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.443

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Abstract PDF

Background

Cancer registries play a fundamental role in cancer control and multicenter collaborative research. Recently, the need for reassessment of cancer registry criteria has arisen due to the newly released 2010 World Health Organization (WHO) classification. Accordingly, development of new coding guidelines for cancer is necessary to improve the quality of cancer registries, as well as to prevent conflicts that may arise when seeking medical insurance compensation.

Methods

With funding from the Management Center for Health Promotion, 35 members of the Gastrointestinal Pathology Study Group and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated in a second workshop for gastrointestinal tumor registration in Korea.

Results

The topics of gastric epithelial tumor, colonic intramucosal carcinoma, neuroendocrine tumor (NET), gastrointestinal stromal tumor (GIST) and appendiceal mucinous tumor were discussed for new coding guidelines. A survey was then conducted among 208 members of the KSP for a consensus of the guidelines proposed in the workshop.

Conclusions

Although a few issues were set aside for further discussion, such as coding for non-gastric GIST and some types of NET, the members agreed upon most of the proposed guidelines. Therefore, we suggest using the newly revised International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) coding guidelines for registering gastrointestinal tumors in Korea.

Citations

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Clinicopathologic Impact of Peptide Hormonal Expression in Rectal Neuroendocrine Tumors
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Markers for Screening Lynch Syndrome Are Reliable and Useful for Identifying the Specimen Mislabeling: Sun-ju Byeon, Jiwoon Choi, Kyung Han Nam, Bo-Gun Jang, Hee Eun Lee, Min A Kim, Woo Ho Kim; Korean J Pathol. 2012;46(2):131-136. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.131

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Abstract PDF

Background

During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs.

Methods

We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123).

Results

The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR<100. In addition, there were 153 cases (60.5%) of LR ranging from 100 to 10,000 and 100 cases (39.5%) of LR>10,000. Furthermore, the combined probability of identity was 9.23×10^-4 and the combined power of exclusion was 0.99908.

Conclusions

Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.

Citations

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Lost, mislabeled, and mishandled surgical and clinical pathology specimens: A systematic review of published literature
Heather J Carmack, Braidyn S Lazenby, Kylie J Wilson, Jamie N Bakkum-Gamez, Leslie Carranza
American Journal of Clinical Pathology.2024; 162(4): 349. CrossRef
Sensitivity and polymorphism of Bethesda panel markers in Chinese population
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Case Report

Undifferentiated Carcinoma Arising in a Choledochal Cyst: A Case Report.: Hee Eun Lee, Chang Lim Hyun, You Jeong Lee, Hye Sil Seol, Ja June Jang; Korean J Pathol. 2006;40(6):461-465.

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Abstract PDF: An association between choledochal cyst and carcinoma is well established. Here, we report an extremely rare case of undifferentiated carcinoma exhibiting extensive sarcomatous features arising in a choledochal cyst. The patient in our case had a radiologically confirmed choledochal cyst and anomalous pancreaticobiliary ductal union, and mild wall thickening in the cyst was observed on endoscopic retrograde cholangiopancreatography. The patient underwent common bile duct excision and cholecystectomy. In the choledochal cyst, a nodule measuring 1.5x1 cm was detected. The lesion was composed of atypical, spindle-shaped and large, round pleomorphic tumor cells simulating sarcoma. Neither glandular nor squamous differentiation was observed. These cells were immunoreactive for both vimentin and cytokeratin by immunohistochemistry. These histologic and immunohistochemical findings were consistent with undifferentiated carcinoma, spindle and giant cell type, according to the WHO classification.

Original Articles

Pathological Analysis of 1,000 Cases of Transrectal Ultrasoundguided Systematic Prostate Biopsy: Establishment of New Sample Processing Method and Diagnostic Utility of Immunohistochemistry.: Chang Lim Hyun, Hee Eun Lee, Haeryung Kim, Hye Seung Lee, So Yeon Park, Jin Haeng Chung, Gheeyoung Choe; Korean J Pathol. 2006;40(6):406-419.

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36 Download

Abstract PDF: BACKGROUND
We developed a new processing method for extended prostate needle biopsy, and evaluated diagnostic utility of routine immunohistochemistry in 1,000 consecutive unselected cases of transrectal ultrasound-guided systematic prostate biopsy.
METHODS
Four to five biopsy cores were embedded in one paraffin block. All the biopsy cores were immunohistochemically stained with basal cell markers.
RESULTS
The new sample processing method was technically perfect for making a diagnosis from extended prostate needle biopsy. Among 1,000 cases, there were 323 cases (32.3%) of adenocarcinoma, 5 cases of other malignant tumors, 9 cases of high-grade prostatic intraepithelial neoplasia without a carcinoma, and only 8 cases of atypical small acinar proliferation. Among the 323 cases of adenocarcinoma, there were 38 cases (11.8%) of microcarcinomas <0.1 cm and 101 cases (31.3%) of small adenocarcinomas <0.3 cm in length. In the needle biopsy specimens, 59 cases (18.3%) were classified as clinically insignificant carcinomas. Among them, 37 cases underwent radical prostatectomy, which turned out to be clinically significant carcinomas in 24 cases (64.9%).
CONCLUSIONS
Routinely performed immunohistochemistry combined with the new sample processing method is very effective for detecting microscopic carcinoma foci as well as differentiating carcinoma from benign conditions mimicking cancer.

Immunohistochemical Characteristics of Kaposi Sarcoma and its Mimicries.: Kyoung Bun Lee, Hye Seung Lee, Hee Eun Lee, So Yeon Park, Jin Haeng Chung, Gheeyoung Choe, Woo Ho Kim, Kye Yong Song; Korean J Pathol. 2006;40(5):361-367.

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Abstract PDF: BACKGROUND
The differential diagnosis of Kaposi sarcoma includes many disease that range from benign disease to malignant tumors. However, little information is available about the immunohistochemical characteristics of Kaposi sarcoma.
METHODS
The expressions of 13 various proteins (HHV-8 LNA-1, Ki-67, bcl-2, p53, CD31, CD34, factor VIII, D2-40, vimentin, SMA, S-100, EMA, and c-kit) were evaluated immunohistochemically in 49 vascular tumors including 16 Kaposi sarcomas, 8 angiosarcomas, 2 hemangioendotheliomas, and 23 benign vascular tumors with using the tissue array method.
RESULTS
All 16 cases of Kaposi sarcoma showed nuclear staining for HHV-8 LNA-1, whereas all the cases of angiosarcoma and benign vascular lesions were negative for HHV-8 LNA-1 (p<0.001). All Kaposi sarcoma were positive for D2-40, which is a marker of lymphatic differentiation, but 25% of the benign vascular lesions and 30.4% of the angiosarcoma were positive for D2-40 (p<0.001). The mean proliferation index as assessed by Ki-67 immunostaining revealed no difference between the benign and malignant vascular lesions (p>0.05). No Kaposi sarcoma showed a bcl-2 expression, but 62.5% of the angiosarcomas and 21.7% of the benign vascular tumors had bcl-2 expressions (p=0.005).
CONCLUSIONS
Immunohistochemical detection of HHV-8 LNA-1 and D2-40 are useful tools to differentiate Kaposi sarcoma from other vascular tumors.

Case Report

Hydrops Fetalis Due to Parvovirus B19 Infection: Report of Two Autopsy Cases.: Ho Chang Lee, Hee Eun Lee, Pil Gyu Hwang, Je G Chi, Sung Hye Park; Korean J Pathol. 2006;40(3):245-249.

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Abstract PDF: Hydrops fetalis (HF) is a disease characterized by generalized subcutaneous edema and cavity effusion in the fetal stage. We report here on two autopsy cases of HF that were caused by parvovirus B19 (PVB19) infection. The human PVB19 is an erythrovirus that cause diverse clinical manifestations ranging from an asymptomatic or mild presentation to more severe effects such as hydrops fetalis, and this is the only known human pathogenic parvovirus. The gestational ages of the two fetuses were 21 weeks and 23 weeks, respectively. Both fetuses were hydropic and anemic. Hepatic tissues of both fetuses demonstrated erythroblasts with eosinophilic intranuclear inclusions, the so called "lantern cells". PVB19 was confirmed by electron microscopy and immunohistochemical staining. For the diagnosis of this disease, recognition of parvovirus infection as a cause of hydrops fetalis and careful examination of red blood cells with a high-power view are required.

Original Article

Pathologic Features of Korean Prostate Adenocarcinoma: Mapping Analysis of 83 Cases.: You Jeong Lee, Dong Il Kim, Hee Eun Lee, Jae Kyung Won, Eun Kyung Hong, Geon Kook Lee, Kang Hyun Lee, Weon Seo Park; Korean J Pathol. 2006;40(3):204-209.

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Abstract PDF: BACKGROUND
:Prostatic adenocarcinoma makes up about 2% of the total cancer incidence and cancer death in Korean men, but the incidence of this malady is continuously increasing. So far, there have been only a few studies describing the pathologic characteristics of the prostatic adenocarcinoma in Korean patients. In this study, we analyzed 83 radical prostatectomy specimens by using mapping analysis to discover the clinico pathologic characteristics of Korean prostatic adenocarcinoma.
METHODS
The resected prostates were serially sectioned and embedded for histologic mapping. The clinico pathologic findings, including the Gleason score, tumor size, prostate intraepithelial neoplasia (PIN) and tumor invasion to the surrounding tissues, were examined.
RESULTS
The mean values were as follows: age, 64.1+/-6.6 years; serum prostate specific antigen (sPSA), 16.6+/-16.2 ng/mL; tumor volume, 22.3+/-22.4%; tumor size, 2.2+/-1.2 cm; and Gleason score, 6.9+/-0.9. The rate of high grade PIN was 79.7%. The Gleason score, tumor extent and T stage were statistically correlated (p<0.05).
CONCLUSIONS
Some prognostic factors such as sPSA and the Gleason scores showed significantly lower levels compared with those of the previous studies on Korean prostate adenocarcinoma (16-36 ng/mL vs 16.6 ng/mL and 7.3-7.7 vs 6.9, respectively). Although these values are still higher than those of the western studies, this study implies that the early detection of prostate adenocarcinoma is increasing in Korea.

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