Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

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2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

CA : A Cancer Journal for Clinicians

Reactive oxygen species

YAP/TAZ at the Roots of Cancer

One-Carbon Metabolism in Health and Disease

The aim of this study was to investigate the expression of glutamine metabolism-related proteins to determine whether glutamine is metabolized differently according to breast cancer molecular subtype. We generated a tissue microarray of 702 breast cancer patients and performed immunohistochemical staining for glutamine metabolism-related proteins, including glutaminase 1 (GLS1 (GLS)), glutamate dehydrogenase (GDH (H6PD)), and amino acid transporter-2 (ASCT2 (SLC1A5)), which were separately evaluated in tumor and stroma compartments and then analyzed by breast cancer molecular subtypes. Breast cancers were classified as follows: 293 luminal A (41.7%), 166 luminal B (23.6%), 67 HER2 type (9.6%), and 176 TNBC (25.1%). HER2 type showed the highest stromal GLS1 (P=0.001), tumoral GDH (P=0.001), stromal GDH (P<0.001), and tumoral ASCT (P<0.001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer.

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Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer.

Local recurrence of phyllodes tumor (PT) of the breast is an adverse outcome that can result in sarcomatous degeneration. The aim of this study was to investigate the histologic and surgical factors associated with local recurrence. A total of 193 PT cases were studied: 145 (75.1 %) benign cases, 33 (17.1 %) borderline cases, and 15 (7.8 %) malignant cases. Stratifying our analysis according to histologic grade, we investigated the relationship between disease-free survival (DFS) and both histologic and surgical factors, including histologic grade, stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, type of surgical procedure (local excision, wide excision, and mastectomy), surgical margin status, and radiation therapy. In the case of benign PT, all patients with local recurrences (3.4 %) had been treated with local excision, and all recurrent tumors were also benign. The local recurrence rate for locally excised benign PTs was not associated with surgical margin status or radiation therapy. In the case of borderline PT, local excision was associated with an increased local recurrence rate (P = 0.046). In malignant PT, small tumor size (≤4.0 cm) was associated with an increased local recurrence rate (P = 0.041). Univariate analyses indicated that surgical procedure (mastectomy < local excision < wide excision; P < 0.001) was significantly associated with shorter DFS in borderline PT. A positive surgical resection margin (P < 0.001) was associated with DFS in malignant PT. The factors associated with local recurrence differed with the histologic grade of PT, as did the features of local recurrence itself. In particular, benign PT had very low rate of local recurrence regardless of surgical margin status or radiation therapy, even when treated with local excision. In the case of benign PT, no recurrent tumors had worse histologic grades than the initial tumors.

Analysis of phyllodes tumor recurrence according to the histologic grade

Introduction
The aim of this study was to investigate the differential expression of markers related to metabolic, mitochondrial and autophagy status in different molecular subtypes of breast cancer.

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Metabolic interaction between cancer cells and stromal cells according to breast cancer molecular subtype.

Aims: To investigate the relationship between the expression of autophagy-related proteins, including beclin-1, light chain (LC) 3A, LC3B, and p62, and prognosis in invasive breast cancer.



Methods and results:   We constructed tissue microarrays from the breast cancer cells of 489 patients, and classified molecular subtypes using surrogate immunohistochemical stains. The tumoral expression levels of LC3A and LC3B were highest in triple-negative breast cancer (TNBC) (P < 0.001), whereas these types of tumour had the lowest expression levels of these markers in the stroma (P = 0.005 and P < 0.001, respectively). Cytoplasmic beclin-1 expression was highest in TNBC, but nuclear expression was lowest (P < 0.001). p62 cytoplasmic and nuclear expression were highest in HER2-type tumours (P = 0.001 and P < 0.001, respectively). Tumoral LC3A and LC3B expression were associated with high histological grade (P < 0.001, and P < 0.028, respectively), but nuclear p62 expression was associated with lower histological grade (P = 0.004).



Conclusions:   Autophagy-related markers are differentially expressed according to the molecular subtype of breast cancer. In particular, expression of LC3A, LC3B and beclin-1 was highest in TNBC tumour cells, whereas that of LC3A and LC3B in the tumour stroma was lowest in TNBC.

Expression of autophagy-related markers beclin-1, light chain 3A, light chain 3B and p62 according to the molecular subtype of breast cancer.

Purpose 
Glycine and serine are well-known, classic metabolites of glycolysis. Here, we profiled the expression of enzymes associated with serine/glycine metabolism in different molecular subtypes of breast cancer and discuss their potential clinical implications.


Methods 
We used western blotting and immunohistochemistry to examine five serine-/glycine-metabolism–associated proteins (PHGDH, PSAT, PSPH, SHMT, and GLDC) in six breast cancer cell lines and 709 breast cancer cases using tissue microarray (TMA).


Results 
PHGDH and PSPH, associated with serine metabolism, were highly expressed in the TNBC cells. GLDC, associated with glycine metabolism, was highly expressed in HER-2-positive MDA-MB-453 and TNBC-related MDA-MB-435S. TMA showed that the TNBC-type breast cancer tissues highly expressed PHGDH, PSPH, and SHMT1, but not the luminal-A-type tissues (p<0.001). PSPH and SHMT1 expression in the tumor stroma of HER-2-type cancers was the highest, but the luminal-A tissues showed the lowest expression (p<0.001). GLDC was most frequently expressed in cancer cells and stroma of the HER-2-positive cancers and least frequently in TNBC (p<0.001). By Cox multivariate analysis, tumor PSPH positivity (hazard ratio [HR]: 2.068, 95% confidence interval [CI]: 1.049–4.079, p = 0.036), stromal PSPH positivity (HR: 2.152, 95% CI: 1.107–4.184, p = 0.024), and stromal SHMT1 negativity (HR: 2.142, 95% CI: 1.219–3.764, p = 0.008) were associated with short overall survival.


Conclusions 
Expression of serine-metabolism–associated proteins was increased in TNBC and decreased in the luminal-A cancers. Expression of glycine-metabolism–associated proteins was high in the tumor and stroma of HER-2-positive cancers.

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0101004&type=printable

Woo Hee Jung

Papers

Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer.

Analysis of phyllodes tumor recurrence according to the histologic grade

Metabolic interaction between cancer cells and stromal cells according to breast cancer molecular subtype.

Expression of autophagy-related markers beclin-1, light chain 3A, light chain 3B and p62 according to the molecular subtype of breast cancer.

Differential Expression of Enzymes Associated with Serine/Glycine Metabolism in Different Breast Cancer Subtypes