Breast Cancer and p16: Role in Proliferation, Malignant Transformation and Progression

The definition of new molecular biomarkers could provide a more reliable approach in predicting the prognosis of invasive breast cancers (IBC). The aim of this study is to analyze the expression of p16 protein in IBC, as well as its participation in malignant transformation. The study included 147 patients diagnosed with IBC. The presence of non-invasive lesions (NIL) was noted in each IBC and surrounding tissue. p16 expression was determined by reading the percentage of nuclear and/or cytoplasmic expression in epithelial cells of IBC and NIL, but also in stromal fibroblasts. Results showed that expression of p16 increases with the progression of cytological changes in the epithelium; it is significantly higher in IBC compared to NIL (p < 0.0005). Cytoplasmic p16 expression is more prevalent in IBC (76.6%), as opposed to nuclear staining, which is characteristic of most NIL (21.1%). There is a difference in p16 expression between different molecular subtypes of IBC (p = 0.025). In the group of p16 positive tumors, pronounced mononuclear infiltrates (p = 0.047) and increased expression of p16 in stromal fibroblasts (p = 0.044) were noted. In conclusion, p16 protein plays an important role in proliferation, malignant transformation, as well as in progression from NIL to IBC.

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Interval Breast Cancers in the NHS Breast Screening Programme: Does the Current Definition Exclude Too Many?

Journal of Medical Screening ◽

10.1177/096914139700400310 ◽

1997 ◽

Vol 4 (3) ◽

pp. 169-173 ◽

Cited By ~ 11

Author(s):

A M Faux ◽

D C Richardson ◽

G M Lawrence ◽

M E Wheaton ◽

M G Wallisconsultant

Keyword(s):

Breast Screening ◽

Interval Cancer ◽

Breast Cancers ◽

Interval Cancers ◽

Exclusion Criteria ◽

National Statistics ◽

Screening Unit ◽

Cancer Rates ◽

Definition Of ◽

The Impact

Objectives— To examine the impact of the definition of interval breast cancers on interval cancer rates arising from the prevalent (first) screening round. Design— Interval breast cancers arising from the prevalent (first) screening round at the Warwickshire, Solihull and Coventry Breast Screening Unit (17 April 1989 to 31 March 1992) were identified by comparison of data held at the unit with records at the West Midlands Cancer Intelligence Unit. Exclusion criteria used in National statistics were applied to this sample to quantify their impact on achieved interval cancer rates. The round lengths experienced by individual women at the unit were determined from the prevalent and incident invitation dates for 155 women with incident (re-screen) breast cancers detected in the second round. Setting— Warwickshire, Solihull and Coventry Breast Screening Unit. Subects—59 017 women screened between 17 April 1989 and 31 March 1992 with a negative screening result and 155 women with incident screen detected cancers. Results— A total of 278 interval cancers were identified, giving an overall rate from the prevalent screening round of 47.1/10 000 women screened. Of these, 213 met the criteria used in the definition of interval cancers for National statistics and were termed “core” interval cancers. The overall “core” interval rate was 36.1/10 000 women screened, similar to interval cancer rates found in the north west of United Kingdom. Thus applying commonly used exclusion criteria produced a 23.4% reduction in the apparent interval cancer rate, with the largest decrease resulting from the exclusion of cancers arising at 36 months or more from the last screen. Conclusions— The exclusion criteria used in the definition of interval cancers have a significant impact on observed interval cancer rates. Of particular concern is the exclusion in the current National definitions of cancers arising at 36 months or more from the last screen, which may mask a problem with significant implications for the success of the NHSBSP.

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The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion

Medical Oncology ◽

10.1007/s12032-014-0867-x ◽

2014 ◽

Vol 31 (3) ◽

Cited By ~ 33

Author(s):

Nina Petrović ◽

Vesna Mandušić ◽

Boban Stanojević ◽

Silvana Lukić ◽

Lidija Todorović ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Invasion ◽

Breast Cancers ◽

Expression Levels ◽

Non Invasive ◽

Breast Cancer Invasion ◽

The Difference

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Abstract 13272: Efficacy and Safety of Non-invasive Renal Denervation Study Using Externally Delivered Focused Ultrasound in Severe Resistant Hypertension

Circulation ◽

10.1161/circ.132.suppl_3.13272 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Roland E Schmieder ◽

John A Ormiston ◽

Petr Neuzil ◽

Zdenek Stárek ◽

Patrick Kay ◽

...

Keyword(s):

Resistant Hypertension ◽

Renal Denervation ◽

Focused Ultrasound ◽

Surrounding Tissue ◽

Renal Nerves ◽

Antihypertensive Medications ◽

Serious Adverse Events ◽

Sound System ◽

Invasive Approach ◽

Non Invasive

Background: Invasive catheter based techniques for renal denervation have been extensively examined in treating patients with resistant hypertension, with mixed results and some periprocedural complications. New evidence suggested that not all renal nerves are in the range of invasive procedures limited to a distance 4 to 6 mm from the lumen. Aims: To evaluate the safety and efficacy of an entirely non-invasive approach to renal denervation using externally delivered focused ultrasound to the peri-renal artery tissue with real time Doppler-based image guidance. Methods and results: Twenty-seven patients with severe, treatment resistant hypertension, defined as persistent systolic blood pressure (BP) > 160 mmHg despite 3 or more antihypertensive medications, were treated non-invasively with the Kona Medical Surround Sound System™. Focused ultrasound energy was delivered to the renal arteries bilaterally and surrounding tissue using Doppler-based imaging and continuous tracking with automatic correction for kidney motion throughout treatment. Patients received conscious sedation during the treatment period. At this time, all patients have completed 24 weeks and 23 patients 52 weeks of follow up. Post-denervation, the mean changes from baseline BP (175/92 mmHg) were -16.8/-8.6 mmHg at 3 weeks, -23.2/-10.8 mmHg at 6 weeks, -29.7/-13.1 mmHg at 12 weeks, -21.6/-8.7 mmHg at 24 weeks and -25.6/-10.1 mmHg at 52 weeks . No serious device-related events have been reported to date. Forty-one percent of subjects (11/27) reported mild back pain immediately following the denervation treatment. The majority of cases (7/11) completely resolved within three days post treatment without any significant intervention and no case was associated with any motor, sensory deficits. Conclusions: This is the first study in humans using a non-invasive renal denervation system in severe resistant hypertension. Results showed clinically meaningful reductions from baseline in office BP through 52 weeks post-denervation. The procedure was well-tolerated with no serious adverse events. This technology should enable patients to benefit from renal denervation therapy without the invasive risks associated with catheter based techniques.

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Prognostic values of L-type amino acid transporter 1 and CD98hc expression in breast cancer

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-206457 ◽

2020 ◽

pp. jclinpath-2020-206457

Author(s):

Masaaki Ichinoe ◽

Tetuo Mikami ◽

Nobuyuki Yanagisawa ◽

Tsutomu Yoshida ◽

Kiyomi Hana ◽

...

Keyword(s):

Breast Cancer ◽

Amino Acid ◽

Invasive Breast Cancer ◽

Poor Prognosis ◽

Growth Factor Receptor ◽

Amino Acid Transporter ◽

Breast Cancers ◽

Non Invasive ◽

Invasive Tumour ◽

Acid Transporter

AimsL-type amino acid transporter 1 (LAT1) is a major Na+-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.MethodsLAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.ResultsHigh levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.ConclusionsLAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

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Immunohistochemical Analysis of BRAF (V600E) Mutation and P16 Expression in Malignant Melanoma in Lagos, Nigeria: A 10-Year Retrospective Study

Journal of Skin Cancer ◽

10.1155/2019/1628247 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

O. Obadofin ◽

K. Badmos ◽

N. Orsi ◽

M. Bipin ◽

O. Rotimi ◽

...

Keyword(s):

Malignant Melanoma ◽

Protein Expression ◽

Immunohistochemical Analysis ◽

Braf V600e Mutation ◽

Breslow Thickness ◽

University Teaching ◽

Braf V600e ◽

Clark Level ◽

P16 Protein ◽

P16 Expression

Background. In Blacks, malignant melanoma (MM) is associated with greater morbidity and mortality compared to Caucasians. MMs with BRAF V600E mutation as well as those with loss of p16 protein expression are associated with aggressive behavior and worse prognosis. Objectives. We determined BRAF (V600E) mutation status and loss of p16 expression in MM cases in Lagos, Nigeria, and correlated these with histopathologic parameters and patients’ age. Methods. Forty-five cases of MM received between January 2005 and December 2014 in the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital were subjected to immunohistochemical studies to determine BRAF V600E mutation and p16 protein expression. These included cutaneous (n=37), musosal (n=3), and ocular MM (n=2) as well as lymph node metastatases (n=3). Results. BRAF (V600E) mutations were detected in 5/45 (11%) while 31/45 (69%) of the cases had loss of p16 expression. No statistically significant association was found between the BRAF (V600E) mutation, loss of p16 expression, and histologic parameters such as histologic variant, Clark level, Breslow thickness, and ulceration. Conclusion. BRAF (V600E) mutation was detected only in a small proportion of cases while loss of p16 expression occurred in most cases which also had high Clark level, high Breslow thickness, and ulceration.

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Malignant transformation of the salivary gland pleomorphic adenoma in myoepithelial carcinoma – the report of two cases

Polski Przegląd Otorynolaryngologiczny ◽

10.5604/01.3001.0013.0617 ◽

2019 ◽

Vol 8 (1) ◽

pp. 52-55

Author(s):

Paulina Szabelska ◽

Anna Rzepakowska ◽

Benedykt Szczepankiewicz ◽

Elżbieta Niemczyk ◽

Ewa Osuch-Wójcikiewicz ◽

...

Keyword(s):

Salivary Gland ◽

Surgical Treatment ◽

Salivary Glands ◽

Pleomorphic Adenoma ◽

Malignant Transformation ◽

Benign Tumor ◽

Complete Recovery ◽

Surrounding Tissue ◽

Carcinoma Ex Pleomorphic Adenoma ◽

Myoepithelial Carcinoma

A multiform adenoma is the most commonly diagnosed benign tumor of the salivary glands. In the majority of patients, surgical resection of the tumor with the adequate surrounding tissue of salivary gland allows for complete recovery. A small percentage of the cases is a recurring pleomorphic adenoma. Even more rarely the diagnosis of carcinoma ex pleomorphic adenoma is made. The study presents two clinical cases of the malignant transformation of pleomorphic adenoma into the myoepithelial carcinoma. The surgical treatment and additional radiotherapy were performed in both cases.

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Embodied Research in Migration Studies

10.1332/policypress/9781447339069.001.0001 ◽

2018 ◽

Author(s):

Elena Vacchelli

Keyword(s):

Qualitative Research ◽

Research Process ◽

Migrant Women ◽

Invasive Approach ◽

Post Colonial ◽

Research Participants ◽

Non Invasive ◽

Colonial Theory ◽

Embodied Research ◽

Definition Of

The definition of data in qualitative research is expanding. This book highlights the value of embodiment as a qualitative research tool and outlines what it means to do embodied research at various points of the research process. It shows how using this non-invasive approach with vulnerable research participants such as migrant, refugee, and asylum-seeking women can help service users or research participants to be involved in the co-production of services and in participatory research. Drawing on both feminist and post-colonial theory, the author uses her own research with migrant women in London, focusing specifically on collage making and digital storytelling, whilst also considering other potential tools for practicing embodied research such as yoga, personal diaries, dance, and mindfulness. Situating the concept of ‘embodiment’ on the map of research methodologies, the book combines theoretical groundwork with actual examples of application to think pragmatically about intersectionality through embodiment.

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ERβ mRNA expression in ERα-negative and triple-negative breast cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.574 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 574-574

Author(s):

Young Choi ◽

Hadong Kim ◽

Tae-Hoon Kim

Keyword(s):

Cyclin D1 ◽

Mrna Expression ◽

Triple Negative ◽

Lymph Node Status ◽

Mrna Levels ◽

Nuclear Staining ◽

Breast Cancers ◽

Proliferating Cells ◽

Ki 67 ◽

Reverse Transcription Pcr

574 Background: ERα is the main prognostic and therapeutic marker in breast cancer (BC). About 30% of BC cases are negative for ER (ERα-) and do not benefit from antiestrogen therapy (TAM). We aim to study ER-beta (ERβ) expression in ERα- and triple negative (TN) cancers to explore alternate pathway of treatment in this cohort. Methods: We studied 67 ERα- BC cases including 44 TN together with 74 ERα +BC cases obtained from patients aged 29 to 97 years old between 2003 and 2010. The histology included 110 intraductal, 12 medullary and 19 other types. 78 cases were grade 3, 52 were grade 2, and 11 were grade 1. RNA was extracted from FFPE and mRNA levels of ERβ isoform and ERα were determined by real-time quantitative reverse transcription PCR. IHC stains were done on TMA the sections for ERα, PR, Her-2, Ki-67, CK5/6 and Cyclin D1. Results: ERβ isoforms were highly expressed in ERα-, TN, basal-like and HER2 type BC cases. ERβ2 was the major ERβ variant expressed. Ki-67 proliferating cells (>20% nuclear staining) were mostly in ERα- rather than ERα+ cases (69.0% vs. 31.0%) as were cyclin D1- cells (82.2% vs. 17.8%). On the other hand, in ERα+ BC, ERα mRNA expression was consistently high and upregulated, and ERβ, low and down regulated, and the ratio of ERα+ to ERβ+ ranged from 3 to 100. ERβ1, 2 and 5 were co-expressed with ERα in 56%, 63%, and 30% of cases, respectively. Overall, ERβ mRNA levels did not show any significant correlation with age, tumor size, lymph node status and histological grades. Conclusions: ERβ-dependent proliferating tumor cells may render them more sensitive to TAM, and increase the effectiveness of TAM and its metabolites in ERα- and TN cases. Increased overall survival after adjuvant TAM ERα-BC may be directly related to ERβ over-expression. ERβ isoform is potential selective therapeutic target in a sub-cohort of ERα- BC. Additionally, when ERβ and ERα are co-expressed, ERβ appears to play a distinct role from its action in ERα- BC. [Table: see text]

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Low Expression of Nuclear Toll-like Receptor 4 in Laryngeal Papillomas Transforming into Squamous Cell Carcinoma

Otolaryngology ◽

10.1177/0194599814549730 ◽

2014 ◽

Vol 151 (5) ◽

pp. 785-790 ◽

Cited By ~ 10

Author(s):

Taru Ilmarinen ◽

Jaana Hagström ◽

Caj Haglund ◽

Eeva Auvinen ◽

Ilmo Leivo ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Malignant Transformation ◽

Squamous Cell ◽

University Hospital ◽

Transformation Rate ◽

Nuclear Staining ◽

Human Immune System ◽

Retrospective Case ◽

Number Of Patients

Objective The malignant transformation rate of recurrent respiratory papillomatosis (RRP), a disease caused by human papillomavirus (HPV), has varied significantly. Cells of the human immune system express toll-like receptors (TLRs) that recognize particles from viruses and bacteria; TLRs are also present on tumor cells, and down-regulation of TLRs has been shown during the progression of HPV-associated neoplasia. The aim of this study was to determine the malignant transformation rate of laryngeal papillomas (LPs) and analyze the potential of TLR2, TLR4, and TLR9 immunoexpression as indicators of the increased cancer risk. Study Design Retrospective case-control study. Setting Department of Otorhinolaryngology–Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Subjects and Methods We reviewed all patients with RRP treated for LPs between 1975 and 2011. Data from the Finnish Cancer Registry confirmed the number of patients diagnosed with laryngeal squamous cell carcinoma (LSCC). Laryngeal tissue specimens from patients developing LSCC were subjected to TLR2, TLR4, and TLR9 immunohistochemistry. Nine patients with RRP without malignant transformation and 19 patients with LSCC without a pre-existing LP served as controls. Results Nine of 324 patients (2.8%) with RRP developed LSCC. The intensity of nuclear staining of TLR4 was significantly lower in LPs transforming into LSCC than in LPs without malignant transformation. The expression of cytoplasmic TLR4 in LSCC correlated with tumor grade and T stage. Cytoplasmic TLR9 expression was significantly lower in LPs than in LSCC. Conclusion The expression of TLR4 may serve as a predictive marker of malignant transformation in LPs. High immunoexpression of cytoplasmic TLR4 in LSCC was associated with a more aggressive disease.

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