BACKGROUND: The clinical significance of coexpression of type 1 growth factor receptor (T1GFR) family members remains largely unknown. The objective of the current study was to determine the frequency and the possible prognostic effect of coexpression of HER‐1, HER‐2, HER‐3, and HER‐4 by breast carcinoma.METHODS: Tissue microarrays were constructed using clinically annotated formalin‐fixed, paraffin‐embedded tumor samples from 242 patients with invasive breast carcinomas with a median 15‐year follow‐up. The levels of TIGFR family members (HER‐1–HER‐4) were measured by immunohistochemistry. K‐means clustering algorithm, as well as univariate (Kaplan–Meier, log‐rank test) and multivariate (Cox regression) survival analyses were applied to the data set.RESULTS: Using univariate analysis, expression of HER‐1, HER‐2, and HER‐3, but not HER‐4, was significantly associated with decreased patient disease‐specific survival (P < 0.05). Kaplan–Meier survival analysis showed that coexpression of ≥ 2 of HER‐1, HER‐2, and HER‐3 in any combination was associated with reduced patient disease‐specific survival compared with single marker expression or no expression (35% vs. 65% vs. 78% 10‐year survival rates, P = 0.001). Using multivariate analysis, expression of ≥ 2 of HER‐1, HER‐2, and HER‐3 was independent of lymph node status and tumor size.CONCLUSIONS: In a cohort of patients with breast carcinoma, the authors observed T1GFR family member coexpression (HER‐1, HER‐2, and HER‐3) to have a negative synergistic effect on patient outcome, independent of tumor size or lymph node status. Thus, coexpression of T1GFR family members identified a subset of patients with a poor disease prognosis who may potentially benefit from therapy simultaneously targeting several T1GFR family members. Cancer 2005. © 2005 American Cancer Society.

Transformation is a term commonly used to describe the biological process in which normal or premalignant cells undergo a change and become cancerous.¹ For thyroid cancer, transformation or anaplastic transformation describes an intratumoral evolution, or progression, from differentiated thyroid cancer (DTC) into anaplastic thyroid carcinoma (ATC).² Differentiated thyroid cancer, which includes papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), accounts for more than 90% of newly diagnosed thyroid malignancies, and with current treatment few individuals die of their disease.³ Even individuals who present with evidence of metastatic DTC can experience long-term survival.⁴ In contrast, ATC is considered one of the most lethal of all human cancers but accounts for less than 2% of all newly diagnosed thyroid malignancies.⁵ Despite advances in the understanding and treatment of human cancer gleaned during the past several decades, little improvement has occurred in the outcomes of individuals diagnosed as having ATC.^6-8 Individuals diagnosed as having ATC tend to present with a rapidly enlarging symptomatic neck mass, and many have evidence of metastatic disease.^6-8 A report that evaluated the outcome of 516 patients with ATC from the National Cancer Institute's Surveillance, Epidemiology, and End Results database found that at presentation 38% of newly diagnosed ATC cases had evidence of either extrathyroidal tumor extension or lymph node invasion and 43% of cases had distant metastasis.⁹ The observed overall cause-specific mortality of this ATC cohort was 68.4% at 6 months and 80.7% at 12 months.⁹ Death from ATC is caused by either local and/or regional disease extension, which leads to suffocation or multiorgan failure as a consequence of overwhelming distant metastatic disease.^6-8 In selected patients with ATC who are able to tolerate aggressive multimodal treatment protocols, local disease may be controlled and death occurs as a consequence of distant metastases.^10,11

(2014). Breast abscess: evidence based management recommendations. Expert Review of Anti-infective Therapy: Vol. 12, No. 7, pp. 753-762. doi: 10.1586/14787210.2014.913982

Background: Post-thyroidectomy haemorrhage occurs in 1–2 per cent of patients, one-quarter requiring bedside clot evacuation. Owing to the risk of life-threatening haemorrhage, previous British Association of Endocrine and Thyroid Surgeons (BAETS) guidance has been that day-case thyroidectomy could not be endorsed. This study aimed to review the best currently available UK data to evaluate a recent change in this recommendation. Methods: The UK Registry of Endocrine and Thyroid Surgery was analysed to determine the incidence of and risk factors for post-thyroidectomy haemorrhage from 2004 to 2018. Results: Reoperation for bleeding occurred in 1.2 per cent (449 of 39 014) of all thyroidectomies. In multivariable analysis male sex, increasing age, redo surgery, retrosternal goitre and total thyroidectomy were significantly correlated with an increased risk of reoperation for bleeding, and surgeon monthly thyroidectomy rate correlated with a decreased risk. Estimation of variation in bleeding risk from these predictors gave low pseudo-R2 values, suggesting that bleeding is unpredictable. Reoperation for bleeding occurred in 0.9 per cent (217 of 24 700) of hemithyroidectomies, with male sex, increasing age, decreasing surgeon volume and redo surgery being risk factors. The mortality rate following thyroidectomy was 0.1 per cent (23 of 38 740). In a multivariable model including reoperation for bleeding node dissection and age were significant risk factors for mortality. Conclusion: The highest risk for bleeding occurred following total thyroidectomy in men, but overall bleeding was unpredictable. In hemithyroidectomy increasing surgeon thyroidectomy volume reduces bleeding risk. This analysis supports the revised BAETS recommendation to restrict day-case thyroid surgery to hemithyroidectomy performed by high-volume surgeons, with caution in the elderly, men, patients with retrosternal goitres, and those undergoing redo surgery.

Anaplastic thyroid carcinoma is the most undifferentiated form of thyroid cancer and one of the deadliest of all adult solid malignancies. Here we report the first genomic and transcriptomic profile of anaplastic thyroid cancer including those of several unique cell lines and outline novel potential drivers of malignancy and targets of therapy. We describe whole genomic and transcriptomic profiles of 1 primary anaplastic thyroid tumor and 3 authenticated cell lines. Those profiles augmented by the transcriptomes of 4 additional and unique cell lines were compared to 58 pairs of papillary thyroid carcinoma and matched normal tissue transcriptomes from The Cancer Genome Atlas study. The most prevalent mutations were those of TP53 and BRAF; repeated alterations of the epigenetic machinery such as frame-shift deletions of HDAC10 and EP300, loss of SMARCA2 and fusions of MECP2, BCL11A and SS18 were observed. Sequence data displayed aneuploidy and large regions of copy loss and gain in all genomes. Common regions of gain were however evident encompassing chromosomes 5p and 20q. We found novel anaplastic gene fusions including MKRN1-BRAF, FGFR2-OGDH and SS18-SLC5A11, all expressed in-frame fusions involving a known proto-oncogene. Comparison of the anaplastic thyroid cancer expression datasets with the papillary thyroid cancer and normal thyroid tissue transcriptomes suggested several known drug targets such as FGFRs, VEGFRs, KIT and RET to have lower expression levels in anaplastic specimens compared with both papillary thyroid cancers and normal tissues, confirming the observed lack of response to therapies targeting these pathways. Further integrative data analysis identified the mTOR signaling pathway as a potential therapeutic target in this disease. Anaplastic thyroid carcinoma possessed heterogeneous and unique profiles revealing the significance of detailed molecular profiling of individual tumors and the treatment of each as a unique entity; the cell line sequence data promises to facilitate the more accurate and intentional drug screening studies for anaplastic thyroid cancer.