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Article ; Online: Benign phyllodes tumor of the vulva.

Venkatesh, Kusuma / Jayanthy, T / Patil, Sharada

Indian journal of pathology & microbiology

2021 Volume 64, Issue 4, Page(s) 863–865

MeSH term(s)	Female ; Humans ; Middle Aged ; Neoplasms/diagnosis ; Neoplasms/surgery ; Phyllodes Tumor/diagnosis ; Phyllodes Tumor/surgery ; Vulva/pathology ; Vulvar Neoplasms/diagnosis ; Vulvar Neoplasms/surgery
Language	English
Publishing date	2021-10-08
Publishing country	India
Document type	Case Reports ; Letter
ZDB-ID	197621-7
ISSN	0974-5130 ; 0377-4929
ISSN (online)	0974-5130
ISSN	0377-4929
DOI	10.4103/IJPM.IJPM_292_20
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Article: Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes.

Snijesh, V P / Nimbalkar, Vidya P / Patil, Sharada / Rajarajan, Savitha / Anupama, C E / Mahalakshmi, S / Alexander, Annie / Soundharya, Ramu / Ramesh, Rakesh / Srinath, B S / Jolly, Mohit Kumar / Prabhu, Jyothi S

Translational oncology

2024 Volume 45, Page(s) 101957

Abstract: Background: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature ...

Abstract	Background: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes. Methods: GRsig was derived from Dexamethasone treated cell lines through a bioinformatic pipeline. Immunohistochemistry assessed GR protein expression. Associations between GRsig and tumor phenotypes (proliferation, cytolytic activity (CYT), immune cell distribution, and epithelial-to-mesenchymal transition (EMT) were explored in public datasets. Single-cell RNA sequencing data evaluated context-dependent GR roles, and a cell type-specific prognostic role was assessed in an independent BC cohort. Results: High GRsig levels were associated with a favorable prognosis across BC subtypes. Tumor-specific high GRsig correlated with lower proliferation, increased CYT, and anti-tumorigenic immune cells. Single-cell data analysis revealed higher GRsig expression in immune cells, negatively correlating with EMT while a positive correlation was observed with EMT primarily in tumor and stromal cells. Univariate and multivariate analyses demonstrated the robust and independent predictive capability of GRsig for favorable prognosis. GR protein expression on immune cells in triple-negative tumors indicated a favorable prognosis. Conclusion: This study underscores the cell type-specific role of GR, where its expression on tumor cells is associated with aggressive features like EMT, while in infiltrating lymphocytes, it predicts a better prognosis, particularly within TNBC tumors. The GRsig emerges as a promising independent prognostic indicator across diverse BC subtypes.
Language	English
Publishing date	2024-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2443840-6
ISSN	1936-5233
ISSN	1936-5233
DOI	10.1016/j.tranon.2024.101957
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Article ; Online: BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

Patil, Akkamahadevi / Patil, Sharada / Anupama, C E / Rajarajan, Savitha / Nimbalkar, Vidya P / Amirtham, Usha / Champaka, G / Suma, M N / Patil, Geetha V / Nargund, Ashwini / Pallavi, V R / Jacob, Linu / Premalatha, C S / Prabhu, Jyothi S

The journal of obstetrics and gynaecology research

2023 Volume 49, Issue 12, Page(s) 2875–2882

Abstract: Aim: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 ... ...

Abstract	Aim: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. Methods: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. Results: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). Conclusion: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.
MeSH term(s)	Humans ; Female ; BRCA1 Protein/genetics ; Neoadjuvant Therapy ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; RNA, Messenger
Chemical Substances	BRCA1 Protein ; RNA, Messenger ; BRCA1 protein, human
Language	English
Publishing date	2023-09-22
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1327307-3
ISSN	1447-0756 ; 1341-8076
ISSN (online)	1447-0756
ISSN	1341-8076
DOI	10.1111/jog.15796
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Article: An androgen receptor regulated gene score is associated with epithelial to mesenchymal transition features in triple negative breast cancers.

Rajarajan, Savitha / Snijesh, V P / Anupama, C E / Nair, Madhumathy G / Mavatkar, Apoorva D / Naidu, Chandrakala M / Patil, Sharada / Nimbalkar, Vidya P / Alexander, Annie / Pillai, Maalavika / Jolly, Mohit Kumar / Sabarinathan, Radhakrishnan / Ramesh, Rakesh S / Bs, Srinath / Prabhu, Jyothi S

Translational oncology

2023 Volume 37, Page(s) 101761

Abstract: Background: Androgen receptor (AR) is considered a marker of better prognosis in hormone receptor positive breast cancers (BC), however, its role in triple negative breast cancer (TNBC) is controversial. This may be attributed to intrinsic molecular ... ...

Abstract	Background: Androgen receptor (AR) is considered a marker of better prognosis in hormone receptor positive breast cancers (BC), however, its role in triple negative breast cancer (TNBC) is controversial. This may be attributed to intrinsic molecular differences or scoring methods for AR positivity. We derived AR regulated gene score and examined its utility in BC subtypes. Methods: AR regulated genes were derived by applying a bioinformatic pipeline on publicly available microarray data sets of AR+ BC cell lines and gene score was calculated as average expression of six AR regulated genes. Tumors were divided into AR high and low based on gene score and associations with clinical parameters, circulating androgens, survival and epithelial to mesenchymal transition (EMT) markers were examined, further evaluated in invitro models and public datasets. Results: 53% (133/249) tumors were classified as AR gene score high and were associated with significantly better clinical parameters, disease-free survival (86.13 vs 72.69 months, log rank p = 0.032) when compared to AR low tumors. 36% of TNBC (N = 66) were AR gene score high with higher expression of EMT markers (p = 0.024) and had high intratumoral levels of 5α-reductase, enzyme involved in intracrine androgen metabolism. In MDA-MB-453 treated with dihydrotestosterone, SLUG expression increased, E-cadherin decreased with increase in migration and these changes were reversed with bicalutamide. Similar results were obtained in public datasets. Conclusion: Deciphering the role of AR in BC is difficult based on AR protein levels alone. Our results support the context dependent function of AR in driving better prognosis in ER positive tumors and EMT features in TNBC tumors.
Language	English
Publishing date	2023-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2443840-6
ISSN	1936-5233
ISSN	1936-5233
DOI	10.1016/j.tranon.2023.101761
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Article ; Online: miR-18a Mediates Immune Evasion in ER-Positive Breast Cancer through Wnt Signaling.

Nair, Madhumathy G / D, Apoorva / M, Chandrakala / Vp, Snijesh / Patil, Sharada / Ce, Anupama / Mukherjee, Geetashree / Kumar, Rekha V / Prabhu, Jyothi S / Ts, Sridhar

Cells

2022 Volume 11, Issue 10

Abstract: ER-positive (ER+) breast cancer is considered immunologically ‘silent’ with fewer tumor-infiltrating immune cells. We have previously demonstrated the role of miR-18a in mediating invasion and poor prognosis in ER+ breast cancer by activation of the Wnt ... ...

Abstract	ER-positive (ER+) breast cancer is considered immunologically ‘silent’ with fewer tumor-infiltrating immune cells. We have previously demonstrated the role of miR-18a in mediating invasion and poor prognosis in ER+ breast cancer by activation of the Wnt signaling pathway. Here, we explored the immune-modulatory functions of high levels of miR-18a in these tumors. A microarray-based gene expression analysis performed in miR-18a over-expressed ER+ breast cancer cell lines demonstrated dysregulation and suppression of immune-related pathways. Stratification of the ER+ tumor samples by miR-18a levels in the TCGA and METABRIC cohort and immune cell identification performed using CIBERSORT and Immune CellAI algorithms revealed a higher proportion of T-regulatory cells (p < 0.001) and a higher CD4/CD8 ratio (p < 0.01). miR-18a over-expressed MCF7 co-cultured with THP-1 showed decreased antigen presentation abilities and increased invasiveness and survival. They also promoted the differentiation of pro-tumorigenic M2 macrophages. Inhibition of the Wnt pathway in miR-18a over-expressed cells brought about the restoration of TAP-1, a protein critical for antigen presentation. Examination of tumor specimens from our case series showed that miR-18a high ER+ tumors had a dense lymphocyte infiltrate when compared to miR-18a low tumors but expressed a higher CD4/CD8 ratio and the M2 macrophage marker CD206, along with the invasive marker MMP9. We report for the first time an association between miR-18a-mediated Wnt signaling and stromal immune modulation in ER+ tumors. Our results highlight the possibility of formulating specific Wnt pathway inhibitors that may be used in combination with immune checkpoint blockers (ICB) for sensitizing ‘immune-cold’ ER+ tumors to immunotherapy.
MeSH term(s)	Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immune Evasion ; MicroRNAs/metabolism ; Wnt Signaling Pathway
Chemical Substances	MIRN18A microRNA, human ; MicroRNAs
Language	English
Publishing date	2022-05-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11101672
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Article: Anaplastic large cell lymphoma: A great mimic on cytology.

Agnihotri, Mona A / Kothari, Kanchan S / Naik, Leena P / Patil, Sharada

Journal of cytology

2016 Volume 34, Issue 3, Page(s) 165–167

Abstract: Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma, accounting for <5% of non-Hodgkin's lymphoma. Cutaneous involvement can be primary or secondary arising in systemic ALCL. The diagnostic feature in both is the presence of pleomorphic, CD30 ... ...

Abstract	Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma, accounting for <5% of non-Hodgkin's lymphoma. Cutaneous involvement can be primary or secondary arising in systemic ALCL. The diagnostic feature in both is the presence of pleomorphic, CD30 positive hallmark cells. We present a case of ALCL in a 19-year-old male presenting as an ulcerated scalp swelling. Clinical impression was actinomycosis or scrofuloderma. Cytology smears showed large dispersed pleomorphic cells with hyperlobated nuclei and multinucleated giant cells. The differentials considered were ALCL, rhabdomyosarcoma, and poorly differentiated carcinoma. Immunocytochemistry (ICC) showed positivity for leukocyte common antigen (LCA) and CD30 while negativity for desmin, favoring ALCL. Computed tomography (CT) showed a lytic paravertebral lesion. Subsequently, both paraspinal and scalp lesions were biopsied and immunochemistry confirmed the diagnosis of ALCL. Thus, cutaneous involvement in ALCL can resemble inflammatory and other neoplastic lesions clinically and cytologically. Hence, a high index of suspicion and ICC can aid in the correct diagnosis on fine needle aspiration cytology (FNAC).
Language	English
Publishing date	2016-09-23
Publishing country	India
Document type	Case Reports
ZDB-ID	645018-0
ISSN	0970-9371
ISSN	0970-9371
DOI	10.4103/0970-9371.208101
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Article: On-site toluidine blue staining and screening improves efficiency of fine-needle aspiration cytology reporting.

Ammanagi, A S / Dombale, V D / Patil, Sharada S

Acta cytologica

2012 Volume 56, Issue 4, Page(s) 347–351

Abstract: Objective: We investigated the role of on-site toluidine blue staining and screening in fine-needle aspiration cytology (FNAC) reporting for patients with thyroid nodules, palpable breast lumps and palpable lymph nodes.: Study design: A total of 200 ... ...

Abstract	Objective: We investigated the role of on-site toluidine blue staining and screening in fine-needle aspiration cytology (FNAC) reporting for patients with thyroid nodules, palpable breast lumps and palpable lymph nodes. Study design: A total of 200 consecutive patients with a palpable lymph node or a lump in the breast or thyroid referred to the outpatient department for FNAC were included in this study. We used toluidine blue to stain FNAC slides for the evaluation of smear adequacy. The toluidine blue-stained slides were compared with the same slides after being decolorised and Papanacolaou (PAP)-stained. Results: Out of 200 cases, 28 (14%) were deemed unsatisfactory on the first attempt as assessed by rapid staining. These included 16 (38%) of 42 thyroid cases, 10 (10.4%) of 96 breast lump cases and 2 (3.2%) of 62 lymph node cases. A repeat FNAC in the same sitting on these 28 patients showed adequate material in 24 (12%) of them. Therefore, for 98%, a decision could be made at the very first visit to plan further management. Conclusions: We concluded that toluidine blue offers excellent cytological details for the preliminary identification of the lesion and to decide on the adequacy of the material for definitive diagnosis on FNAC slides.
MeSH term(s)	Biopsy, Fine-Needle ; Breast Neoplasms/diagnosis ; Breast Neoplasms/surgery ; Coloring Agents ; Cytological Techniques/methods ; Female ; Humans ; Lymphatic Metastasis/diagnosis ; Male ; Pathology, Surgical/methods ; Staining and Labeling/methods ; Thyroid Nodule/diagnosis ; Thyroid Nodule/surgery ; Tolonium Chloride
Chemical Substances	Coloring Agents ; Tolonium Chloride (15XUH0X66N)
Language	English
Publishing date	2012
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80003-x
ISSN	1938-2650 ; 0001-5547
ISSN (online)	1938-2650
ISSN	0001-5547
DOI	10.1159/000338725
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Article: On-Site Toluidine Blue Staining and Screening Improves Efficiency of Fine-Needle Aspiration Cytology Reporting

Ammanagi, A.S. / Dombale, V.D. / Patil, Sharada S.

Acta Cytologica

2012 Volume 56, Issue 4, Page(s) 347–351

Institution	Department of Pathology, S.N. Medical College, Bagalkot, India
Abstract	Objective: We investigated the role of on-site toluidine blue staining and screening in fine-needle aspiration cytology (FNAC) reporting for patients with thyroid nodules, palpable breast lumps and palpable lymph nodes. Study Design: A total of 200 consecutive patients with a palpable lymph node or a lump in the breast or thyroid referred to the outpatient department for FNAC were included in this study. We used toluidine blue to stain FNAC slides for the evaluation of smear adequacy. The toluidine blue-stained slides were compared with the same slides after being decolorised and Papanacolaou (PAP)-stained. Results: Out of 200 cases, 28 (14%) were deemed unsatisfactory on the first attempt as assessed by rapid staining. These included 16 (38%) of 42 thyroid cases, 10 (10.4%) of 96 breast lump cases and 2 (3.2%) of 62 lymph node cases. A repeat FNAC in the same sitting on these 28 patients showed adequate material in 24 (12%) of them. Therefore, for 98%, a decision could be made at the very first visit to plan further management. Conclusions: We concluded that toluidine blue offers excellent cytological details for the preliminary identification of the lesion and to decide on the adequacy of the material for definitive diagnosis on FNAC slides.
Keywords	Fine-needle aspiration cytology ; Toluidine blue ; Rapid stain ; Papanacolaou stain
Language	English
Publishing date	2012-07-25
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Fine Needle Aspiration
ZDB-ID	80003-x
ISSN	1938-2650 ; 0001-5547
ISSN (online)	1938-2650
ISSN	0001-5547
DOI	10.1159/000338725
Database	Karger publisher's database

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