Prevalence and Clinical Significance of Preoperative Thyroglobulin Antibodies in Differentiated Thyroid Cancer Patients

Thyroglobulin antibody (TgAb) has been used as a surrogate tumor marker of differentiated thyroid carcinoma (DTC) patients. Preoperative TgAb (PreopTgAb) is thought to affect the prevalence, disease severity, and outcome of DTC. The objective of the present study was to retrospectively analyze the prevalence of PreopTgAb in patients diagnosed with DTC and its relation to thyroid cancer characteristics, staging, and disease outcome. A retrospective analysis of 109 DTC patients with reports of PreopTgAb was carried out. Clinicopathological parameters, including patient demographics (age and gender), TNM staging, histopathologic characteristics (type of pathology, vascular invasion, extrathyroid extension, carcinoma variant, multifocality), treatment (surgery, radioactive iodine), and outcome were recorded. The association of PreopTgAb was compared with the study variables and outcome of the disease using the Chi-square test and Mann-Whitney tests. The prevalence of PreopTgAb was 59.6%. Among the 54 PreopTgAb positive patients, 34 patients had an excellent response and 15 patients had an indeterminate response, while biochemically and structurally incomplete response was observed in 3 and 2 patients, respectively. PreopTgAb was not significantly associated with age (p = 0.919), sex (p = 0.650), pathology (p = 0.079), stage at diagnosis (p = 0.513), vascular invasion (p = 0.211), extra thyroid extension (p = 0.734), histologic variant (p = 0.877), multifocality (p = 0.361), and outcome (p = 0.360). Although we did not find a significant association between positive PreopTgAb and clinical characteristics and outcome of DTC, it can still be considered as a surrogate marker of DTC during follow-up.

Molecular typing guiding treatment and prognosis of endometrial cancer

Genetic abnormalities,such as PTEN,PIK3CA,CTNNB1,ARID1A,and ERBB2,which frequently occur in endometrial cancer(EC),are potential therapeutic targets.In 2013,integrated genomic analysis conducted by The Cancer Genome Atlas identified four molecular subtypes,including POLE ultra-mutated,microsatellite instability hypermutated,copy-number low,and copy-number high,which strongly correlate with prognosis.Surrogate markers-based molecular classification methods have been developed to make these molecular classifications accessible and affordable,achieving classification into POLEmut,mismatch repair deficient(MMRd),p53abn,and no specific molecular profile(NSMP)with normal p53 expression.Although POLEmut EC has aggressive pathologic features,there are few cases of advanced and/or recurrence.Therefore,the possibility of de-escalating adjuvant therapy can be considered.Additionally,immune checkpoint inhibitors(ICI)may be a candidate for treating advanced and recurrent POLEmut EC because of their high immunogenicity.MMRd EC shows an intermediate prognosis between those of POLEmut and p53abn EC.MMRd EC is generally characterized by high immunogenicity similar to POLEmut EC,suggesting that ICI can also be a potential therapeutic agent.Among the four molecular subtypes,p53abn EC has the worst prognosis.However,some p53abn tumors have the molecular hallmark of homologous recombination deficiency and could be treated with poly(ADP-ribose)polymerase inhibitors.In addition,some p53abn tumors overexpress the human epidermal growth factor receptor 2,which can also be a potential therapeutic target.NSMP EC are a heterogeneous population because they lack characteristic molecular biological features.Approximately half of the NSMP EC show high expression of estrogen receptor/progesterone receptor,suggesting the possibility of hormonal therapy.In addition,the PI3K/AKT/mTOR pathway frequently altered in EC may be a therapeutic target.This review summarizes the molecular biological characteristics and potential therapeutic agents in molecularly featured EC.Several clinical trials are in progress to stratify EC into molecular classifications and demonstrate the efficacy and safety of molecularly matched treatment and management strategies.