Clinicopathological and Prognostic Significance of Programmed Death Ligand 1 Expression in Korean Patients With Triple-negative Breast Carcinoma

Kim, Hyunsoo; Im, Sung Il; Kim, Dong-Hoon; Apple, Sophia K.

doi:10.21873/anticanres.14093

Cited by 15 publications

(18 citation statements)

References 58 publications

(76 reference statements)

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“…Immune evasion should be the cause of clinical behavior of this tumor, because activation of the PD-1/PD-L1pathway decreases proliferation and increases apoptosis of the intratumoral immune cells. Confirmed by Kim et al and our studies, PD-L1 was expressed in the intratumoral immune cells in almost half cases of TNBC [13]. By the way, there are two antibodies, PD-L1(SP142) and PD-L1(SP263), available for PD-L1 detection for tumor cells and intratumoral immune cells.…”

Section: Discussionsupporting

confidence: 87%

PTEN May Involve in Regulation of PD-L1 Expression in Triple Negative Breast Carcinoma

Wai

Chan

Vong

et al. 2021

OJMS

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Triple negative breast carcinoma (TNBC) is a rapid progressive tumor and has a poor overall survival. Therefore, it is crucial to find out effective molecular targets and develop optimal therapeutic strategies for TNBC. In this study, immunohistochemical staining was used to detect expressions of programmed death-ligand 1 (PD-L1) and phosphatase and tensin homolog (PTEN) in 136 breast carcinomas including 50 TNBC. The effect of PTEN on regulation of PD-L1 expression was assessed in vitro in the PTEN knockdown TNBC cells. We found that PD-L1(SP142) positive rate in TNBC (48.0%) was significantly higher than non-TNBC (23.3%). PTEN negative rate was 42% in TNBC. The inverse correlation between PTEN and PD-L1(SP142) expression in TNBC was statistically significant (P<0.05). After PTEN knockdown, PD-L1 expression in TNBC cells increased significantly, and the expression level of AKT increased simultaneously. PTEN knockdown promoted cell proliferation, viability and G1/S switch of TNBC cells. These results suggested that PTEN may involve in regulation of PD-L1 expression, because PTEN loss can upregulate PD-L1 expression in TNBC. Antitumor immunity of PD-L1 could be enhanced in TNBC when targeting PTEN at the same time.

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Section: Discussionsupporting

confidence: 87%

PTEN May Involve in Regulation of PD-L1 Expression in Triple Negative Breast Carcinoma

Wai

Chan

Vong

et al. 2021

OJMS

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“…Immunohistochemical staining. Immunostaining was performed using an automated immunostainer (Ventana BenchMark XT, Ventana Medical Systems, Tucson, AZ, USA) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). After antigen retrieval, 4-μm-thick, formalin-fixed, paraffin-embedded slices were incubated with primary antibodies, including p16 (prediluted, clone E6H4, Ventana Medical Systems), p40 (1:100, polyclonal, Biocare Medical, Concord, CA, USA), carcinoembryonic antigen (CEA; 1:200, clone II-7, Dako, Glostrup, Denmark), erb-b2 (prediluted, clone 4B5, Ventana Medical Systems), and PD-L1 (prediluted, clone 22C3, Agilent Technologies, Santa Clara, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Uterine Cervix: Clinicopathological and Molecular Characteristics With Special Emphasis on the First Description of Consistent Programmed Death-ligand 1 (PD-L1) Over-expression

Choi

Kim

2021

Cancer Genomics Proteomics

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Background/Aim: Invasive stratified mucinproducing carcinoma (ISMC) of the uterine cervix has been reported to be more aggressive than other subtypes of endocervical adenocarcinoma. We investigated the clinicopathological and molecular characteristics of eight ISMCs. Patients and Methods: We reviewed the electronic medical records and pathology slides of eight patients with ISMC and conducted programmed death-ligand 1 (PD-L1) immunostaining and targeted sequencing. Results: The patients were between 31 and 54 years. Six tumors were pure ISMCs, and two showed co-existing squamous cell carcinoma and usual-type endocervical adenocarcinoma. Lymph node metastases were detected in three cases. Three patients developed distant metastases to the adnexa, lungs, inguinal lymph nodes, and small intestine. Two patients experienced disease progression, and three developed postoperative local recurrences. All tumors showed PD-L1 over-expression, with a mean combined positive score of 73.8 (range=30-100). One tumor harbored erb-b2 receptor tyrosine kinase 2 amplification. Conclusion: ISMC of the uterine cervix exhibits a high risk of recurrence, metastasis, and resistance to chemoradiation therapy. PD-L1 overexpression was consistently observed in all ISMCs. This finding raises the possibility that patients with ISMC may benefit from PD-L1 immunotherapy.Stratified mucin-producing intraepithelial lesion (SMILE) is a newly described premalignant lesion of the uterine cervix. This lesion is believed to arise in the embryonic or reserve cells in the transformation zone. In addition to cervical highgrade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS), the well-known premalignant intraepithelial lesions, SMILE is associated with high-risk human papillomavirus (HPV) infection (1). This uncommon lesion is histologically characterized with stratified columnar epithelial cells possessing intracytoplasmic mucin throughout the entire epithelial thickness (1), and is classified as a variant of AIS in the 2014 World Health Organization Classification of Tumours of Female Genital Tumours (2). HSIL and AIS often co-exist with SMILE, and squamous cell carcinoma and usual-type endocervical adenocarcinoma are associated with 10-50% of SMILE cases (1, 3, 4). In 2016, Lastra et al. (5) described a distinctive subtype of invasive endocervical adenocarcinoma exhibiting morphological features similar to those of SMILE as an invasive stratified mucin-producing carcinoma (ISMC) or invasive SMILE. ISMC comprises approximately 10% of endocervical adenocarcinoma cases and less than 1% of all cervical carcinoma cases. It is the third most common subtype of 685 This article is freely accessible online.

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“…Immunostaining was performed to confirm our diagnosis, as previously described (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). A panel of antibodies against Wilms tumor 1 (WT1), p53, estrogen receptor (ER), paired box 8 (PAX8), PAX2, GATA-binding protein 3 (GATA3), and P16 was used.…”

Section: Case Reportmentioning

confidence: 99%

Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma

Kim

Bae

Jung

et al. 2021

In Vivo

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Background/Aim: We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC). Case Report: A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA. Conclusion: Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.Ovarian carcinoma is the deadliest gynecological malignancy, accounting for more than 14,000 deaths each year (1). Highgrade serous carcinoma (HGSC) is the most prevalent and aggressive subtype of ovarian carcinoma, accounting for 70% of ovarian carcinoma-related deaths. The fallopian tube has recently emerged as an important site of origin not only for tubo-ovarian HGSC in patients with germline mutation of breast cancer 1 (BRCA1) or BRCA2, but also as a source of peritoneal HGSC (2). A thorough histological examination of resected ovaries and fallopian tubes has led researchers to focus on investigating the carcinogenesis of tubo-ovarian HGSC from the fallopian tube. Increasing evidence suggests that the distal part of the fallopian tube, particularly the fimbria, is the origin of tubo-ovarian and peritoneal HGSCs, and serous tubal intraepithelial carcinoma (STIC) is the precursor lesion (3). STIC is morphologically characterized by the proliferation of non-ciliated epithelium, showing stratification, loss of polarity, severe nuclear pleomorphism, conspicuous nucleoli, and increased mitotic activity (1, 4). In addition to these histological criteria, more than 90% of STICs harbor mutations of tumor protein 53 (TP53), resulting in aberrant expression of p53 on immunostaining. Therefore, the lesions typically demonstrate either p53 overexpression (indicating missense mutations) or complete absence of p53 staining (indicating nonsense or frameshift mutations) (5).

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Clinicopathological and Prognostic Significance of Programmed Death Ligand 1 Expression in Korean Patients With Triple-negative Breast Carcinoma

Cited by 15 publications

References 58 publications

PTEN May Involve in Regulation of PD-L1 Expression in Triple Negative Breast Carcinoma

PTEN May Involve in Regulation of PD-L1 Expression in Triple Negative Breast Carcinoma

Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Uterine Cervix: Clinicopathological and Molecular Characteristics With Special Emphasis on the First Description of Consistent Programmed Death-ligand 1 (PD-L1) Over-expression

Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma

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