Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer

Aziz, Sura; Wik, Elisabeth; Knutsvik, Gøril; Klingen, Tor Audun; Chen, Ying; Davidsen, Benedicte; Aas, Hans; Aas, Turid; Akslen, Lars A.

doi:10.1371/journal.pone.0150979

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…HER2-SISH was performed on IHC 2+ cases, and considered positive if HER2/Chr17 ratio by SISH was > 2.0. Tumors were stained for ER and PR, and considered positive if ≥10% of tumor nuclei stained positive [ 33 ]. Breast tumors diagnosed after 2012 (n cases = 89) were analyzed using immunohistochemistry for hormone receptor status and Ki67, and immunohistochemistry and fluorescence in situ hybridization for HER2.…”

Section: Methodsmentioning

confidence: 99%

Impact of pre-diagnostic triglycerides and HDL-cholesterol on breast cancer recurrence and survival by breast cancer subtypes

et al. 2018

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BackgroundHigh triglycerides and low levels of high density lipoprotein (HDL)-cholesterol are observed to promote tumor growth. However, whether breast cancer heterogeneity may explain the contradictory influence of triglycerides and cholesterol observed on breast cancer prognosis remains unclear.MethodsA population-based survival study among 464 breast cancer cases identified within the Tromsø study was conducted. Pre-diagnostic triglycerides, total-cholesterol and HDL-cholesterol were measured, and detailed clinical and histopathological data were obtained. Using tissue microarray, all breast cancer cases were reclassified into the following subtypes: Luminal A, Luminal B, HER2-enriched, and triple negative breast cancer (TNBC). Multivariable Cox proportional hazards regression models were used to study the associations between pre-diagnostic lipids and breast cancer recurrence, mortality, and survival.ResultsA total of 464 breast cancer patients, with mean age at diagnosis of 57.9 years, were followed for a mean 8.4 years. TNBC patients in the highest tertile of triglycerides (≥ 1.23 mmol/l) had 3 times higher overall mortality compared to TNBC patients in the lowest tertile (≤ 0.82 mmol/l) (HR 2.99, 95% CI 1.17–7.63), and the 5-year overall survival was 19% lower for TNBC patients in the highest vs. lowest tertile of triglycerides (65% vs. 84%). TNBC patients in the highest tertile of the HDL-cholesterol/total-cholesterol ratio (≥0.35), compared to those in the lowest tertile (≤0.27), had a 67% reduced overall mortality risk (HR 0.33, 95% CI 0.12–0.89). No associations were observed between lipids and prognostic outcome among breast cancer patients overall, or among patients with luminal A and luminal B subtypes. Among HER2-enriched patients, pre-diagnostic triglyceride level was inversely associated with overall mortality.ConclusionOur study suggests that pre-diagnostic triglycerides and the HDL-cholesterol/total-cholesterol ratio may independently provide unique information regarding prognostic outcome among triple negative breast cancer patients. However, a small sample size underlines the need for additional studies.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4568-2) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Impact of pre-diagnostic triglycerides and HDL-cholesterol on breast cancer recurrence and survival by breast cancer subtypes

et al. 2018

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“…Hordaland and Vestfold counties have approximately 730,000 inhabitants, representing about 15% of the population in Norway. As the number of node positive cases was initially small in these subseries separately ( n = 139 of 534 for Hordaland; n = 92 of 282 for Vestfold), and since patients from these series showed similar clinico-pathologic characteristics, the two subseries were merged [ 18 ]. For validation purposes, the marker of particular interest in this study, PD-ENE, was studied in these subseries separately, as patients were treated in two different institutions in Norway.…”

Section: Methodsmentioning

confidence: 99%

Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

et al. 2017

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Presence of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218), as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996–2009). Sections were reviewed for the largest metastatic tumor diameter (TD-MET), nodal afferent and efferent vascular invasion (AVI and EVI), extra-nodal extension (ENE), number of ENE foci, as well as circumferential (CD-ENE) and perpendicular (PD-ENE) diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT) diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS) or breast cancer specific survival (BCSS). Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value) in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively). To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer.

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“…Mitotic cells in basal layer of mouse tongues were counted as the number of mitoses per 10 high- power fields (HPF)(400x magnification) for either WT or H3K36M mice 50 , respectively. The number of visualized salivary gland was counted from both WT and H3K36M mice.…”

Section: Methodsmentioning

confidence: 99%

H3K36M provokes cellular plasticity to drive aberrant glandular formation and squamous carcinogenesis

Anderson

Zou

et al. 2022

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Epigenetic dysregulation is pervasive in cancer, frequently impairing normal tissue development and differentiation1. Beyond alterations in histone modifying enzymes, 'oncohistone' mutations have been described across a variety of cancers2-4, although the in vivo effects and underlying mechanisms behind these observations have not been well-studied and remain unclear. Here, by inducing the in vivo expression of histone H3.3 carrying a lysine to methionine (K to M) mutation at position 36 (H3K36M) in self-renewing stratifying epithelial tissues, we show that the H3K36M oncohistone dramatically disrupts normal epithelial differentiation, leading to extensive tissue dysplasia characterized by a significant increase in mitotic, proliferative basal stem cells. Furthermore, this differentiation blockade promotes increased cellular plasticity and enrichment of alternate cell fates, and in particular the aberrant generation of excessive glandular tissue including both hypertrophic salivary, sebaceous, and meibomian glands. Upon carcinogen stress, H3K36M mice display markedly enhanced squamous tumorigenesis. These aberrant phenotypic and gene expression manifestations are associated with global loss of H3K36me2 and concomitant gain of H3K27me3. Collectively, these results have revealed a previously unknown critical role for H3K36 methylation in both the in vivo maintenance of proper epithelial cell fate decisions and the prevention of squamous carcinogenesis. Additionally, they suggest that H3K36 methylation modulation may offer new avenues for the regulation of numerous common disorders driven by over- or under-active glandular function.

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Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer

Cited by 11 publications

References 42 publications

Impact of pre-diagnostic triglycerides and HDL-cholesterol on breast cancer recurrence and survival by breast cancer subtypes

Impact of pre-diagnostic triglycerides and HDL-cholesterol on breast cancer recurrence and survival by breast cancer subtypes

Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

H3K36M provokes cellular plasticity to drive aberrant glandular formation and squamous carcinogenesis

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