Cell polarity and cell adhesion associated gene expression differences between invasive micropapillary and no special type breast carcinomas and their prognostic significance

Kramer, Zsófia; Kenessey, István; Gángó, Ambrus; Lendvai, Gábor; Kulka, Janina; Tőkés, Anna-Mária

doi:10.1038/s41598-021-97347-8

Cited by 3 publications

(10 citation statements)

References 71 publications

(77 reference statements)

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“…Significant differences have been identified in mRNA expressions of integrin-β1 (ITGB1), integrin-α1 (ITGA1), RAC1, CLDN1, SLUG/SNAI2, ZEB1, DLG1, CLDN4, CDH1 (E-cadherin), OCLN, CLDN7, AFDN/ AF6, CLDN3, LIN7A which are effective in cell polarity in MPCs (Table 3). 59,60 Integrin is a protein that forms the glandular lumen and maintains polarity in epithelial cells. Its aberrant expression is associated with adhesion, angiogenesis, tumor progression, and metastasis.…”

Section: Mrna Expressionmentioning

confidence: 99%

“…Claudins are integral membrane proteins, and CLDN1, CLDN3, CLDN4, and CLDN7 significantly lower expression levels are shown in IMPC cases. 59 The Crumbs complex plays an essential role in the apical polarity complex. PALS (proteins associated with LIN7) and PATJ (Pals1-associated tight junction) are the proteins that make up this complex.…”

Section: Mrna Expressionmentioning

confidence: 99%

“…It has been determined that the LIN7A gene is overexpressed in IMPCs, and this expression has a role in the invasion and loss of apicobasal polarity. 59,65 Interestingly, LIN7A is required for human epidermal growth factor receptor 2 (HER2) localization on the basolateral surface of cells. Micropapillary areas may show loss of HER2 expression concerning LIN7A, and a lower HER2 score can be seen immunohistochemically.…”

Section: Mrna Expressionmentioning

confidence: 99%

“…This finding suggests that IMPC tumor cell clusters appear in a highly epithelial state and that these tumor cells form clusters during the stromal invasion and metastasis for- mation rather than using the traditional EMT pathway used by IBC-NSTs. 59 Jagged-1 is the most critical ligand in the Notch signaling pathway and has been associated with poor prognosis and metastasis in breast carcinomas. Jagged-1 regulates EMT by reducing E-cadherin expression.…”

Section: Mrna Expressionmentioning

confidence: 99%

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Molecular Pathology of Micropapillary Carcinomas: Is Characteristic Morphology Related to Molecular Mechanisms?

Yilmaz

Sarıoğlu

2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Micropapillary carcinoma is an entity defined histologically in many organs. It is associated with lymph node metastasis and poor prognosis. The main mechanism for its histopathologic appearance is reverse polarization. Although the studies on this subject are limited, carcinomas with micropapillary morphology observed in different organs are examined by immunohistochemical and molecular methods. Differences are shown in these tumors compared with conventional carcinomas regarding the rate of somatic mutations, mRNA and miRNA expressions, and protein expression levels. TP53, PIK3CA, TERT, KRAS, EGFR, MYC, FGFR1, BRAF, AKT1, HER2/ERBB2, CCND1, and APC mutations, which genes frequently detected in solid tumors, have also been detected in invasive micropapillary carcinoma (IMPC) in various organs. 6q chromosome loss, DNAH9, FOXO3, SEC. 63, and FMN2 gene mutations associated with cell polarity or cell structure and skeleton have also been detected in IMPCs. Among the proteins that affect cell polarity, RAC1, placoglobin, as well as CLDNs, LIN7A, ZEB1, CLDN1, DLG1, CDH1 (E-cadherin), OCLN, AFDN/AF6, ZEB1, SNAI2, ITGA1 (integrin alpha 1), ITGB1 (integrin beta 1), RHOA, Jagged-1 (JAG1) mRNAs differentially express between IMPC and conventional carcinomas. Prediction of prognosis and targeted therapy may benefit from the understanding of molecular mechanisms of micropapillary morphology. This review describes the molecular pathologic mechanisms underlying the micropapillary changes of cancers in various organs in a cell polarity-related dimension.

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Section: Mrna Expressionmentioning

confidence: 99%

Section: Mrna Expressionmentioning

confidence: 99%

Section: Mrna Expressionmentioning

confidence: 99%

Section: Mrna Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Pathology of Micropapillary Carcinomas: Is Characteristic Morphology Related to Molecular Mechanisms?

Yilmaz

Sarıoğlu

2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…A recent study by Kramer et al showed that IMPC tumor cells were in a highly epithelial state and did not use the EMT pathway, but rather form cell clusters during invasion and metastasis. 82 …”

Section: Lymphovascular Invasion and Lymph Node Involvementmentioning

confidence: 99%

Micropapillary Breast Carcinoma: From Molecular Pathogenesis to Prognosis

GI¹,

Tchabashvili²,

Mulita³

et al. 2022

BCTT

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Invasive micropapillary carcinoma (IMPC) of the breast is an infrequent type of breast cancer often discussed for its potency for lymphovascular invasion and difficulty in accurate imaging estimation. Micropapillary carcinomas are noted to be present as larger tumors, of higher histological grade and a notably higher percentage of disease-positive lymph nodes. Hormonal and HER-2 positivity in IMPC is also commoner when compared to other NST carcinomas. IMPC occurs either as a pure form or more often as a component of mixed Non-Specific Type (NST) carcinoma. The latest data suggest that despite having comparable survival rates to other histological subtypes of breast carcinoma, effective surgical treatment often requires extended surgical margins and vigilant preoperative axillary staging due to an increased incidence of lymph node invasion, and locoregional recurrence. Moreover, the presence of micropapillary in situ components within tumors also seems to alter tumor aggression and influence the nodal disease stage. In this review, we present an overview of the current literature of micropapillary carcinoma of the breast from biology to prognosis, focusing on biological differences and treatment.

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Chromophobe Renal Cell Carcinoma With Extensive Retraction Artifact: A Potential Diagnostic Pitfall From Micropapillary Urothelial Carcinoma

Sangoi,

Pivovarcikova,

Akgul

et al. 2024

Int J Surg Pathol

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In addition to “classic” and eosinophilic subtype, chromophobe renal cell carcinoma (RCC) is well-known to demonstrate various morphological patterns including adenomatoid, microcystic, pigmented, multicystic, papillary, neuroendocrine-like, and small cell-like, all of which are important to appreciate for accurate diagnosis. Herein, we expand on a unique chromophobe RCC morphology not previously described consisting of tumor cells with extensive stromal retraction, mimicking upper urothelial tract micropapillary carcinoma (MPC). Twelve MPC-like chromophobe RCC nephrectomies were reviewed with clinicopathological features recorded; molecular testing was performed on 7 of 12 tumors. Patients were mostly men (n=10) with a mean age of 65 years. Mean tumor size was 6.4 cm with pathological stage distribution as follows: 4 (33%) T1a, 2 (17%) T1b, 1 (8%) T2b, and 3 (25%) T3a. The extent of MPC-like chromophobe RCC foci ranged from 10% to 40% (mean=26%; there was no correlation between the extent of MPC-like chromophobe RCC foci and tumor stage). Other chromophobe RCC morphological patterns were not identified. When performed, all (100%) tumors depicted prototypic chromophobe RCC staining pattern of KIT positivity/KRT7 positivity. Molecular showed 6 of 7 (86%) with multiple chromosomal losses. Clinically significant mutations were identified in NF1, TP53, FLCN (likely somatic), CHEK2, and ZFHX3 genes. Follow up available in 9 patients showed no evidence of disease (mean=23 months). Although the etiology behind the extensive stromal retraction in our tumors is unknown, this may likely be artifactual in nature. Nonetheless, it is important to include MPC-like chromophobe RCC in the spectrum of “variant” morphologies to avoid diagnostic pitfalls from micropapillary carcinoma.

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Cell polarity and cell adhesion associated gene expression differences between invasive micropapillary and no special type breast carcinomas and their prognostic significance

Cited by 3 publications

References 71 publications

Molecular Pathology of Micropapillary Carcinomas: Is Characteristic Morphology Related to Molecular Mechanisms?

Molecular Pathology of Micropapillary Carcinomas: Is Characteristic Morphology Related to Molecular Mechanisms?

Micropapillary Breast Carcinoma: From Molecular Pathogenesis to Prognosis

Chromophobe Renal Cell Carcinoma With Extensive Retraction Artifact: A Potential Diagnostic Pitfall From Micropapillary Urothelial Carcinoma

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