Journal of Pathology and Translational Medicine

Original Articles

Immunohistochemical expression in idiopathic inflammatory myopathies at a single center in Vietnam: Dat Quoc Ngo, Si Tri Le, Khanh Hoang Phuong Phan, Thao Thi Phuong Doan, Linh Ngoc Khanh Nguyen, Minh Hoang Dang, Thien Thanh Ly, Thu Dang Anh Phan; J Pathol Transl Med. 2024;58(4):174-181. Published online June 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.05.02

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Abstract PDF: Background
The identification of idiopathic inflammatory myopathies (IIMs) requires a comprehensive analysis involving clinical manifestations and histological findings. This study aims to provide insights into the histopathological and immunohistochemical aspects of IIMs.
Methods
This retrospective case series involved 56 patients diagnosed with IIMs at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, from 2019 to 2023. The histology and immunohistochemical expression of HLA-ABC, HLA-DR, C5b-9, Mx1/2/3, and p62 were detected.
Results
We examined six categories of inflammatory myopathy, including immunemediated necrotizing myopathy (58.9%), dermatomyositis (DM; 23.2%), overlap myositis (8.9%), antisynthetase syndrome (5.4%), inclusion body myositis (IBM; 1.8%), and polymyositis (1.8%). The average age of the patients was 49.7 ± 16.1 years, with a female-to-male ratio of 3:1. Inflammatory cell infiltration in the endomysium was present in 62.5% of cases, perifascicular atrophy was found in 17.8%, and fiber necrosis was observed in 42 cases (75.0%). Rimmed vacuoles were present in 100% of cases in the IBM group. Immunohistochemistry showed the following positivity rates: HLA-ABC (89.2%), HLA-DR (19.6%), C5b-9 (57.1%), and Mx1/2/3 (10.7%). Mx1/2/3 expression was high in DM cases. p62 vacuole deposits were noted in the IBM case. The combination of membrane attack complex and major histocompatibility complex I helped detect IIMs in 96% of cases.
Conclusions
The diagnosis of IIMs and their subtypes should be based on clinical features and histopathological characteristics. Immunohistochemistry plays a crucial role in the diagnosis and differentiation of these subgroups.

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer: Hong Sik Park, Uiju Cho, So Young Im, Chang Young Yoo, Ji Han Jung, Young Jin Suh, Hyun Joo Choi; J Pathol Transl Med. 2019;53(2):75-85. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.11

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Background
Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.
Methods
We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.
Results
Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort.
Conclusions
Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Citations

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Daniel S. Lefler, Steven A. Manobianco, Babar Bashir
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HLA-I and breast cancer prognosis: A systematic review and meta-analysis
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Cancer Immunology: Immune Escape of Tumors—Expression and Regulation of HLA Class I Molecules and Its Role in Immunotherapies
Yuan Wang, Simon Jasinski-Bergner, Claudia Wickenhauser, Barbara Seliger
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In Silico Pipeline to Identify Tumor-Specific Antigens for Cancer Immunotherapy Using Exome Sequencing Data
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HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events
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14-bp Insertion/Deletion Polymorphism of the HLA-G Gene in Osteosarcoma Patients.: Ahrim Moon, Su Kang Kim, Joo Ho Chung, Ki Yong Na, Liliana G Olvi, Eduardo Santini-Araujo, Youn Wha Kim, Yong Koo Park; Korean J Pathol. 2011;45(5):485-490.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.485

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Abstract PDF

BACKGROUND
The major histocompatibility complex class I, G (human leukocyte antigen-G [HLA-G]) gene plays a vital role in the suppression of immune responses. Recently, a number of studies have reported an association between HLA-G and diseases (pregnancy complications, organ transplantation, and tumors). Some of the studies have revealed that the 14-bp insertion/deletion polymorphism might be associated with various diseases. The aim of the present study was to explore a possible influence of the 14-bp insertion/deletion polymorphism on osteosarcoma.
METHODS
Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tumor tissues derived from patients with conventional osteosarcoma (OSA) and 183 peripheral blood samples of healthy controls. Fifty-eight cases were South Korean patients with OSA and 17 cases were Argentine patients with OSA. The HLA-G 14-bp insertion/deletion polymorphism at exon 8 of the HLA-G locus was analyzed by polymerase chain reaction.
RESULTS
There was a significantly different distribution profile for the 14-bp genotypes between the Korean OSA and Korean control groups. Specifically, there were more heterozygote 210 bp/224 bp genotypes in the Korean OSA group when compared to the Korean control group (62.1% vs 40.4%, p=0.002).
CONCLUSIONS
The results suggest that HLA-G heterozygote patients may be more susceptible to OSA in the Korean population.

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14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran
Mehdi Haghi, Mohammad Ali Hosseinpour Feizi, Majid Sadeghizadeh, Abbas Sahebghadam Lotfi
Asian Pacific Journal of Cancer Prevention.2015; 16(14): 6155. CrossRef

Immunohistochemical Analysis of HLA-DR and Secretory Component Expression in Gastric Adenocarcinoma.: Ji Youn Bae, Soo Sang Sohn, Eun Sook Chang; Korean J Pathol. 1996;30(4):293-300.

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Abstract PDF: Sixty one cases of gastric adenocarcinoma were studied immunohistochemically for expression of HLA-DR and secretory component(SC) in order to analyze the relationship between expression of these in gastric cancer cells and the adjacent mucosa. Immunostaining was detected within the cytoplasm and on the cell memgrane. The rate of HLA-DR and SC expressions in cancer cells were 59.0% and 49.2%, respectively, and 52.5%/52.5% and 31.2%/50.8% the mucosa in adjacent/remote from the site of to cancer. The SC expression in the adjacent mucosa was lower than that of the remote mucosa(p=0.027). The HLA-DR expression in the cancer cells in the intestinal type of gastric adenocarcinoma(73.9%) was higher than that of the diffuse type(14.3%) and it was statistically significant(p=0.02). The presence of an increased amount of lymphoid infiltration in the gastric mucosa was closely related to the expression of HLA-DR and SC. Decreased or absent expression of SC at the transitional mucosal cells was possibly a result of exposure to genotoxic agents due to the lack of protective function of SC-IgA. From these results, one can postulate that the expression of HLA-DR and SC may play an important role in atleration in microenvironment with lymphoid infiltration.

Interdigitating Reticulum Cell Sarcoma of Lymph Node.: Sung Suk Paeng, Yoon Ju Kim, Seong Eun Yang, Duck Hwan Kim, Hee Jin Chang, Jung Il Suh, Chu Woo Kim; Korean J Pathol. 1996;30(7):635-642.

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Abstract PDF: We report a case of reticulum cell sarcoma in the right cervical lymph node of a 42-year-old male. It was a slowly growing, non-tender movable mass of 8 months duration. Microscopically, the lymph node was effaced by proliferating spindle cells arranged in broad sheets, bands, or fascicular patterns in paracortical area sparing of B-cell region. The tumor component was divided by fibrous band. The individual cells had oval to round or elongated nuclei, with inconspicuous nucleoli and moderate amounts of cytoplasms with indistinct cell borders. Pleomorphic large cells with binucleated, or multinucleated bizarre nuclei with prominent nucleoli, were partly admixed. In immunohistochemical stain, the tumor cell was strong positive for S-100 protein, HLA-DR, Mac387 and weakly positive for Leukocyte common antigen and equivocal for Vimentin. But it was negative for CD21, Ki-1, Desmin, Epithelial membrane antigen and Cytokeratin. These immunohistochemical findings suggested that the neoplastic cell was originated from the interdigitating reticulum cell of lymph node. The patient was treated by radiation therapy, and alive well at 37 months of follow-up.

The Expression of C4d and HLA-DR in Renal Allografts with the Histologic Features of Antibody-Mediated Rejection.: Young Soo Song, Moon Hyang Park; Korean J Pathol. 2008;42(5):260-269.

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Abstract PDF: BACKGROUND
Deposition of C4d along the peritubular capillaries is generally associated with an antibody-mediated response. We evaluated, with performing C4d immunostaining, the diagnostic accuracy of the cases that were previously diagnosed as antibody-mediated rejection (ABMR) when based only on the histologic findings, and we examined possible correlation of C4d with HLA-DR.
METHODS
Forty-five renal transplantation biopsies, which showed ABMR-like histology, were obtained. The expressions of C4d and HLA-DR in the transplant rejection cases were investigated using immunofluorescent and/or immunohistochemical staining. RESULTS: There were 14 discordant cases among a total of 45 cases when C4d was used as a diagnostic marker and the original slides were reviewed. These total cases consisted of the C4d negative cases in two cases of hyperacute rejection and all the cases of ABMR and ABMR with chronic/sclerosing allograft nephropathy (CAN) and two C4d positive cases (one each of acute cellular rejection (ACR) and CAN according to their original diagnosis) and all these cases were then revised according to Banff 07. The expression of HLA-DR tended to be correlated with the log-transformed duration of grafts until three years after the transplantation. CONCLUSION: This study demonstrates that C4d together with the histologic findings should be used for making the diagnosis of ABMR. The tubular HLA-DR expression over time should be studied to further understand the mechanism of graft rejection.

Expression of ras Oncogene Product, MHC class II Antigen and Human Papillomavirus 16/18 DNA in Carcinomas of the Uterine Cervix.: K J Cho, Ja June Jang; Korean J Pathol. 1993;27(5):485-490.

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Abstract PDF: Immunohistochemical study for ras oncogene product(p21) and MHC class II(HLA-DR) antigen, and in situ hybridization for human papillomavirus(HPV) type 16/18 were performed on 50 squamous cell carcinomas of the uterine cervix. Activated ras and aberrant DR expression were noted in 26 cases(52%) and 11 cases(22%), respectively, without a difference between keratinizing and non-keratinizing types. No direct correlation between ras and DR expression was histologically found. p21 was diffusely distributed with a finely granular pattern in the cytoplasm. Aberrant DR expression was also diffuse, with linear staining along the cell membrane. In situ hybridization revealed HPV type 16/18 DNAs in superficial koilocytotic cells of 4 cases, in which ras or DR expression was not correlated with the presence of HPV DNA.

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