factor 1α in precancerous nodules with telomere

Increased expression of stathmin and elongatio

Concordant or Discordant? Imaging-Pathology Correlation in a Sonography-Guided Core Needle Biopsy of a Breast Lesion

An imaging-guided core needle biopsy has been proven to be reliable and accurate for the diagnosis of both benign and malignant diseases of the breast, and has replaced surgical biopsy. However, the possibility of a false-negative biopsy still remains. Imaging-pathology correlation is of critical importance in imaging-guided breast biopsies to detect such a possible sampling error and avoid a delay in diagnosis. We will review five possible categories and corresponding management after performing an imaging-pathology correlation in a sonography-guided core needle biopsy of a breast lesion, as well as illustrate the selected images for each category in conjunction with the pathologic finding. Radiologists should be familiar with the imaging features of various breast pathologies and be able to appropriately correlate imaging findings with pathologic results after a core needle biopsy

Hepatogastric fistula caused by direct invasion of hepatocellular carcinoma after transarterial chemoembolization and radiotherapy

A 63-year-old man with a history of hepatitis-B-related hepatocellular carcinoma (HCC) in the left lateral portion of the liver received repeated transcatheter arterial chemoembolization (TACE) and salvage radiotherapy. Two months after completing radiotherapy, he presented with dysphagia, epigastric pain, and a protruding abdominal mass. Computed tomography showed that the bulging mass was directly invading the adjacent stomach. Endoscopy revealed a fistula from the HCC invading the stomach. Although the size of the mass had decreased with the drainage through the fistula, and his symptoms had gradually improved, he died of cancer-related bleeding and hepatic failure. This represents a case in which an HCC invaded the stomach and caused a hepatogastric fistula after repeated TACE and salvage radiotherapy

Cancer as a Metabolic Disorder

Cancer has long been considered a genetic disease characterized by a myriad of mutations that drive cancer progression. Recent accumulating evidence indicates that the dysregulated metabolism in cancer cells is more than a hallmark of cancer but may be the underlying cause of the tumor. Most of the well-characterized oncogenes or tumor suppressor genes function to sustain the altered metabolic state in cancer. Here, we review evidence supporting the altered metabolic state in cancer including key alterations in glucose, glutamine, and fatty acid metabolism. Unlike genetic alterations that do not occur in all cancer types, metabolic alterations are more common among cancer subtypes and across cancers. Recognizing cancer as a metabolic disorder could unravel key diagnostic and treatments markers that can impact approaches used in cancer management

Expression of Pentose Phosphate Pathway-Related Proteins in Breast Cancer

Purpose. The purpose of this study was to assess the expression of pentose phosphate pathway- (PPP-) related proteins and their significance in clinicopathologic factors of breast cancer. Methods. Immunohistochemical staining for PPP-related proteins (glucose-6-phosphate dehydrogenase [G6PDH], 6-phosphogluconolactonase [6PGL], 6-phosphogluconate dehydrogenase [6PGDH], and nuclear factor-erythroid 2-related factor 2 [NRF2]) was performed using tissue microarray (TMA) of 348 breast cancers. mRNA levels of these markers in publicly available data from the Cancer Genome Atlas project and Kaplan-Meier plotters were analyzed. Results. Expression of G6PDH and 6PGL was higher in HER-2 type (p<0.001 and p=0.009, resp.) and lower in luminal A type. 6PGDH expression was detected only in TNBC subtype (p<0.001). G6PDH positivity was associated with ER negativity (p=0.001), PR negativity (p=0.001), and HER-2 positivity (p<0.001), whereas 6PGL positivity was associated with higher T stage (p=0.004). The 562 expression profile from the TCGA database revealed increased expression of G6PDH and 6PG in the tumor compared with normal adjacent breast tissue. The expression of G6PDH was highest in HER-2 type. HER-2 and basal-like subtypes showed higher expression of 6PGDH than luminal types. Conclusion. PPP-related proteins are differentially expressed in breast cancer according to molecular subtype, and higher expression of G6PDH and 6PGL was noted in HER-2 subtype

Multifaceted Roles of Interleukin-6 in Adipocyte–Breast Cancer Cell Interaction

Breast cancer is the most common malignancy in women worldwide, with a developmental process spanning decades. The malignant cells recruit a variety of cells including fibroblasts, endothelial cells, immune cells, and adipocytes, creating the tumor microenvironment. The tumor microenvironment has emerged as active participants in breast cancer progression and response to treatment through autocrine and paracrine interaction with the malignant cells. Adipose tissue is abundant in the breast cancer microenvironment; interactions with cancer cells create cancer-associated adipocytes which produce a variety of adipokines that influence breast cancer initiation, metastasis, angiogenesis, and cachexia. Interleukin (IL)-6 has emerged as key compound significantly produced by breast cancer cells and adipocytes, with the potential of inducing proliferation, epithelial-mesenchymal phenotype, stem cell phenotype, angiogenesis, cachexia, and therapeutic resistance in breast cancer cells. Our aim is to present a brief knowledge of IL-6’s role in breast cancer. This review summarizes our current understanding of the breast microenvironment, with emphasis on adipocytes as key players in breast cancer tumorigenesis. The effects of key adipocytes such as leptin, adipokines, TGF-b, and IL-6 are discussed. Finally, we discuss the role of IL-6 in various aspects of cancer progression

Clinicopathologic features of molecular subtypes of triple negative breast cancer based on immunohistochemical markers

This study was performed to identify molecular subtypes of triple negative breast carcinoma (TNBC) based on immunohistochemical markers. We prepared a tissue microarray from TNBC specimens of 122 patients and performed immunohistochemical staining for cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor (AR), and gammma-glutamyltransferase (GGT1). Based on immunoreactivity, tumors were classified into basal-like (CK5/6 positive and/or EGFR positive), molecular apocrine (AR positive and/or GGT1 positive), claudin low (claudin 3, claudin 4, claudin 7 negative and/or E-cadherin negative), mixed (tumors belonging to two or more subtypes), and null (tumors not matching any other subtypes). The TNBC specimens of 122 patients included 27 basal-like (22.1%), 28 claudin low (23.0%), 12 molecular apocrine (9.8%), 23 mixed (18.9%) and 32 null (26.2%) subtype tumors. The molecular apocrine subtype showed the highest percentage of apocrine differentiation and the lowest Ki-67 labeling index (p<0.001 and p=0.040, respectively). In univariate analysis, tumor cell discohesiveness was related with shorter disease free survival (DFS) and overall survival (OS) (p=0.005, and 0.002, respectively). In multivariate analysis, tumor cell discohesiveness was related with shorter OS and CK5/6 positivity (p=0.018), and claudin 7 positivity (p=0.019) was related with shorter DFS. In conclusion, using immunohistochemical staining for CK5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, AR, and GGT1, we categorized TNBC into a basal-like subtype, a claudin low subtype, a molecular apocrine subtype, a mixed subtype showing characteristics of two different subtypes, and a null subtype not belonging to any of the subtypes identified

The role of tumor-associated macrophage in breast cancer biology

Breast cancer is the most commonly diagnosed malignant tumor in women worldwide and contributes significantly as the primary cause of female cancer related mortality. Hence, research is focused on discovering new and effective treatment targets. The breast tumor microenvironment (TME) comprising of recruited host stromal cells and tumor cells, has recently emerged as an important player in tumor progression, with the potential for future treatment. The TME comprises immune system elements (such as macrophages and lymphocytes), cells composing blood vessel, fibroblast, myofibroblast, mesenchymal stem cells, adipocytes and extracellular matrix (ECM). Among these cells, tumor-associated macrophages (TAM) are the prominent components of TME in breast cancers. Macrophages exhibit a high plasticity in response to various external signals and participate in innate and adoptive immune responses to control numerous factors of TME. Depending on the microenvironmental signal present, macrophages are polarized into two distinct phenotypes, the classically activated (M1) or the alternative activated (M2) macrophages. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. In human breast carcinomas, high TAM density correlates with poor prognosis. Over the years, studies into the role of TAMs in breast cancer progression have identified TAMs to be capable of inducing angiogenesis, remodelling the tumor extracellular matrix to aid invasion, modelling breast cancer cells to evade host immune system and recruiting immunosuppressive leukocytes to the tumor microenvironment. Along with these functions, the potential role for TAMs in activation of breast cancer stem cells (CSC) has also emerged. Thus, TAMs in breast cancer can enhance cancer cell invasion by degrading the ECM, stimulate tumor vascularization and angiogenesis and suppress the antitumor functions of cytotoxic T cells resulting in poor prognosis for patients. These observations make TAMs an attractive target for therapeutic intervention by targeting various aspects of their function. This review discusses the mechanisms responsible for TAM recruitment and highlights the roles of TAMs in regulating tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, the potential for TAM-targeted therapy as a promising novel strategy is also discussed

The expression of succinate dehydrogenase in breast phyllodes tumor

The purpose of this study is to investigate the expression of succinate dehydrogenase (SDH)A, SDHB, and HIF-1α in phyllodes tumors and the association with clinic-pathologic factors. Using tissue microarray (TMA) for 206 phyllodes tumor cases, we performed immunohistochemical stains for SDHA, SDHB, and HIF-1α and analyzed their expression in regard to clinicopathologic parameters of each case. The cases were comprised of 156 benign, 34 borderline, and 16 malignant phyllodes tumors. The expression of stromal SDHA and epithelial- and stromal- SDHB increased as the tumor progressed from benign to malignant (P<0.001). There were five stromal SDHA-negative cases and 31 stromal SDHB-negative cases. SDHB negativity was associated with a lower histologic grade (P=0.054) and lower stromal atypia (P=0.048). Univariate analysis revealed that a shorter disease free survival (DFS) was associated with stromal SDHB highpositivity (P=0.013) and a shorter overall survival (OS) was associated with high-positivity of stromal SDHA and SDHB (P<0.001 and P<0.001, respectively). The multivariate Cox analysis with the variables stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, stromal SDHA expression, and stromal SDHB expression revealed that stromal overgrowth was associated with a shorter DFS (hazard ratio: 24.78, 95% CI: 3.126-196.5, P=0.002) and a shorter OS (hazard ratio: 176.7, 95% CI: 8.466-3691, P=0.001). In conclusion, Tumor grade is positively correlated with SDHA and SDHB expression in the tumor stroma in phyllodes tumors of the breast. This result may be attributed to the increased metabolic demand in high grade tumors

Evaluation of the Expression of Amine Oxidase Proteins in Breast Cancer

We aimed to evaluate the expression of amine oxidase proteins in breast cancer and their clinical implications. We performed immunohistochemical staining of amine oxidase proteins (LOX, lysyl oxidase, AOC3, amine oxidase, MAOA, monoamine oxidase A, MAOB, monoamine oxidase B). Based on their hormone receptors, such as estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 immunohistochemical staining, breast cancer was divided into four molecular subtypes: luminal A, luminal B, HER-2 type, and triple-negative breast cancer (TNBC). Luminal A was observed in 380 cases (49.4%), luminal B in 224 (29.1%), HER-2 type in 68 (8.8%), and TNBC in 98 (12.7%). Stromal AOC3, MAO-A, and MAO-B expression varied according to molecular subtypes. Stromal AOC3 expression was high in luminal B and HER-2 type and MAO-A expression was high in luminal A and luminal B (p &lt; 0.001). MAO-B expression was higher in TNBC than in other subtypes (p = 0.020). LOX positivity was associated with high histological grade (p &lt; 0.001) and high Ki-67 labeling index (LI) (p = 0.009), and stromal AOC3 positivity was associated with high histological grade (p = 0.001), high Ki-67 LI (p &lt; 0.001), and HER-2 positivity (p = 0.002). MAO-A positivity was related to low histological grade (p &lt; 0.001), ER positivity, PR positivity (p &lt; 0.001), and low Ki-67 LI (p &lt; 0.001). In univariate analysis, MAO-A positivity was related to short disease-free survival in HER-2 type (p = 0.013), AOC3 negativity was related to short disease-free survival and overall survival in ER-positive breast cancer, PR-positive breast cancer, HER-2-negative breast cancer, and lymph node metastasis. In conclusion, the expression of amine oxidase proteins varies depending on the molecular subtype of breast cancer. Stromal AOC3 expression was high in luminal B and HER-2 type, and MAO-A expression was high in luminal A and luminal B