Association of thyroid autoantibodies with aggressive characteristics of papillary thyroid cancer: a case-control study.

PURPOSE: Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown. PATIENTS AND METHODS: We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC. RESULTS: In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes. CONCLUSION: Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis.

The effects of iodine 131 treatment on chromosomal and oxidative DNA damage in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy.

Serum cholesterol levels are inversely associated with the risk of malignancy in subjects with Bethesda category IV thyroid nodules.

INTRODUCTION: Some epidemiological data suggest that there may be an inverse relationship between cholesterol levels and the risk of thyroid cancer in the overall population. The present study was aimed to evaluate the lipid profile specifically in subjects with Bethesda category IV thyroid nodules, and compare whether there were any differences between those with benign and malignant nodules. METHODS: Single-centre, retrospective study on 204 subjects treated by partial or total thyroidectomy for excision of a Bethesda category IV thyroid nodule, who had undergone a blood lipid profile test in the 12 months prior to surgery. In addition to lipid measures, other demographic, clinical, biochemical and ultrasound data were collected. RESULTS: Seventy-five subjects (36.8%) were diagnosed with thyroid carcinoma in the definitive histopathological examination. Patients with thyroid cancer had lower levels of total cholesterol, LDL-cholesterol and non-HDL-cholesterol than subjects with benign thyroid diseases. There were no differences in HDL-cholesterol, triglycerides or total cholesterol/HDL-cholesterol ratio. There were no differences either between groups in other clinical, biochemical and ultrasound variables, including the use of lipid-lowering drugs. In multivariate analysis, only LDL-cholesterol was independently associated with malignancy. Subjects with follicular carcinoma showed the lowest cholesterol levels, while those with papillary carcinoma had intermediate values between the group with follicular carcinoma and the group with benign thyroid diseases. CONCLUSIONS: In subjects with cytologically indeterminate Bethesda category IV thyroid nodules, levels of total cholesterol, non-HDL-cholesterol and, particularly, LDL-cholesterol are lower among those with malignant nodules.

Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients. We studied n=183 consecutive patients with a diagnosis of PTC which were treated with total thyroidectomy plus 131I ablation. During a follow-up of in mean 97 months, most of the PTC patients had no signs of tumor relapse (n=157 patients). In contrast, one patient had serum Tg levels above the detection limit and<1 ng/ml, two patients Tg serum levels≥1 ng/ml and<2 ng/ml and n=23 patients had Tg serum levels≥2 ng/ml. Morphological signs of tumor recurrence were seen in 14 patients; all of these patients had serum Tg levels≥2 ng/ml. Importantly, with the exception of one patient, all TgAb positive PTC patients (n=27) had no signs of tumor recurrence as the serum Tg levels were below the assays functional sensitivities. Tetramer analyses revealed a higher number of tumor epitope-specific CD8+T cells in TgAb positive patients compared to TgAb negative PTC patients. In summary, we show that the occurrence of TgAbs may have an impact on the clinical outcome in PTC patients. This might be due to a tumor epitope-specific cellular immunity in PTC patients.

Preoperative Serum Thyroglobulin Levels Predict Radioiodine Therapy Outcome in Papillary Thyroid Microcarcinoma Patients.

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10-20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT.

The impact of intraoperative neural monitoring during papillary thyroid cancer surgery on completeness of thyroidectomy and thyroglobulin response: a propensity-score matched study.

BACKGROUND: Intraoperative neural monitoring (IONM) has been utilized for a variety of thyroid pathologies, including papillary thyroid carcinoma (PTC). Remnant thyroid tissue following total thyroidectomy (TT) in patients with PTC is associated with increased recurrence. The aim of this study is to investigate whether the use of IONM in PTC surgery has an impact on the completeness of thyroidectomy. METHODS: Retrospectively, patients with preoperative diagnosis of PTC, who underwent TT in a tertiary center were reviewed. They were grouped based on the IONM usage, and 1:1 propensity-score match was performed. Primary outcome was the completeness of thyroidectomy, determined by measuring postoperative stimulated thyroglobulin levels (sTg). RESULTS: Among 274 clinically node-negative PTC patients who underwent TT and ipsilateral prophylactic central lymph-node dissection, a total of 170 patients (85:85) were matched. Postoperative sTg levels were significantly lower in the IONM group (1 ng/dL vs. 0.4 ng/dL; p < 0.01) with higher percentage of the patients with sTg levels <1 ng/ml (50.6% vs. 69.4%; p = 0.01). More patients in the no-IONM group received RAI ablation with significantly higher doses (mean mci: 120 vs. 102; p = 0.02). CONCLUSION: The use of IONM during thyroidectomy provides improvement in the completeness of thyroidectomy and reduction in postoperative sTg levels which can be used as a guide by clinicians to avoid RAI ablation in selected PTC patients and to adjust low ablative doses in patients who are scheduled for remnant ablation.

The diagnostic predictive value of neutrophil-to-lymphocyte ratio in thyroid cancer adjusted for tumor size.

The role of systemic inflammation has not been clearly defined in thyroid cancers. There have been conflicting reports on whether systemic inflammatory markers have predictive value for thyroid cancers. We aimed to evaluate the association between systemic inflammatory markers and clinicopathological factors in thyroid cancers and to assess their predictive value for thyroid cancers in detail. Five hundred thirty-one patients who underwent surgery for thyroid nodules were included. The patient population consisted of 99 individuals (18.6%) with benign thyroid nodules and 432 individuals (81.4%) with thyroid cancers. In 432 patients with thyroid cancers, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in the cases with tumors greater than 2 cm than in those with tumors less than 2 cm. (p = 0.027). NLR and platelet-to-lymphocyte ratio (PLR) were significantly higher in cases with lateral lymph node metastasis (LNM) than in those without LNM (p = 0.007 and 0.090, respectively). The nodule size was significantly higher in benign thyroid nodules than in thyroid cancers (p < 0.001). When the cases were stratified by tumor size, NLR was a significant predictor of thyroid cancers in cases with nodules greater than 2 cm (Exp(B) = 1.85, 95% CI = 1.15-2.97, p = 0.011), but not in those with nodules less than 2 cm. In thyroid cancers, preoperative NLR was associated with pathological prognosticators such as tumor size and lateral lymph node metastasis. When the size difference between thyroid cancers and benign thyroid nodules was adjusted, NLR could be a significant predictor of thyroid cancers.

Metástasis raras de cáncer papilar de tiroides en músculo esquelético: serie de casos / Rare metastases of papillary thyroid cancer in skeletal muscle: case series

Las metástasis del carcinoma papilar de tiroides (CPT) generalmente son a nivel locorregional, la diseminación a distancia es poco habitual, sin embargo la invasión de tejidos blandos aunque inusual puede ocurrir, y afecta negativamente la supervivencia. El presente estudio describe una serie de casos de Metástasis Musculares de CPT. Se realizó un estudio transversal de un solo centro que evaluó diez pacientes con CPT con metástasis en músculo. La edad de los pacientes fue entre 46 a 77 años, siendo la edad promedio de 60 años, 7 de los cuales fueron de sexo masculino que corresponde al 70%, todos con antecedente de CPT con respuesta estructural incompleta, además de las metástasis en músculo presentaron afectación de tres o más órganos, con necesidad de varios tratamientos, cada paciente registró entre 1 a 8 cirugías, recibieron entre 100 a 780mCi de I131 (yodo radiactivo), ocho ameritaron radioterapia, todos tuvieron indicación de tratamiento con ITK, sin embargo solo cuatro pacientes tuvieron acceso a dicho medicamento. La mayoría de las metástasis del CPT en músculo fueron diagnosticadas en los estudios de imagen PET/ CT, después de la tiroidectomía el tiempo de su presentación fue muy variable entre 1 a 18 años, el número de músculos comprometidos se reporta entre uno a cuatro, siendo el glúteo (4 casos) el músculo metastásico más frecuente. La presencia de metástasis musculares empeora el pronóstico en nuestra serie de pacientes.

Metastases of thyroid papillary carcinoma (CPT) are generally at the locoregional level, the dissemination from a distance is unusual, however the invasion of soft tissues, although rare can occur, and it negatively affects survival. The present study describes several Muscular Metastases of CPT cases. A transversal study in one only center was performed and assessed ten patients CPT metastases in muscles.The patients age ranged from 46 to 77, being the average age of 60, and 7 of them were male, corresponding to the 70%, everyone with CPT records with an incomplete structural response. Besides muscular metastases they also presented issues with three or more organs, needing many treatments. Each patient registered between 1 to 8 surgeries, they received between 100 to 780mCi of I131. Eight required radiotherapies, everyone required treatment with ITK, however, just four patients had access to that medication. Most of the CPT metastases in muscles were diagnosed in PET/CT image studies, after the thyroidectomy, the time for its presentation was very variable between 1 to 18 years, the number of compromised muscles is reported between one to four, being the buttock (4 cases) the most frequently muscle with metastases. The presence of muscular metastases aggravates the prognosis in our series of patients.

Correlation between serum circRNA and thyroid micropapillary carcinoma with cervical lymph node metastasis.

The study aims to characterize the circular RNA (circRNA) expression profile that is functionally related with the invasiveness of papillary thyroid microcarcinoma (PTMC).A total of 13 pairs of female patients with non-invasive PTMC or lymph node metastasis PTMC (PTMC (L)) were included and the serum RNA was obtained. CircRNA microarray was performed to identify the circRNA expression profile. Real time-PCR was used to verify circRNA expression. Bioinformatic approaches were adopted to annotate the function of differentially expressed circRNAs and construct the circRNA-miRNA-mRNA network.In total, 400 significantly upregulated and 290 significantly downregulated circRNAs were identified in PTMC (L) compared with PTMC. Among them, 10 circRNAs were selected and validated by real time-PCR. Putative microRNAs (miRNAs) that could bind to the differentially expressed circRNAs were predicted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of target genes of the differentially expressed circRNAs revealed that these circRNAs may play an important role in lymph node metastasis. Finally, circRNA targeted miRNAs were predicted and a circRNA-miRNA-mRNA network was constructed for hsa_circRNA_404686.Our results showed that several circRNAs, such as hsa_circRNA_404686, may serve as promising diagnostic marker for PTMC (L) in female.

A Blood-based Gene-expression Scoring System for Cancer Screening in Patients With Branch-duct Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: In patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), we aimed to develop a novel blood-based biomarker utilizing a gene-expression profile for the detection of pancreatic malignancies, such as IPMN-derived carcinoma (IPMC) or pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We enrolled 40 patients with pancreatic tumors (24 BD-IPMNs, four IPMCs and 12 PDACs) and identified the characteristic gene-expression profiles in pancreatic malignancies. Subsequently, we constructed a gene-expression scoring system for the proper diagnosis of pancreatic malignancies. The result was validated in 14 patients (five IPMNs, three IPMCs and six PDACs). RESULTS: The scoring system utilizing the expression levels of 13 genes showed high diagnostic yield (sensitivity=94.0%, specificity=92.0% and area under the curve=0.94), which was confirmed in the validation set. Furthermore, its diagnostic yield was not reduced even in early-stage pancreatic malignancies (sensitivity=85.0%, specificity=93.0% and area under the curve=0.88). CONCLUSION: We developed a blood-based gene expression scoring system for cancer screening in patients with BD-IPMNs.

Plasma-Derived miRNA-222 as a Candidate Marker for Papillary Thyroid Cancer.

We analyzed five miRNA molecules (miR-221; miR-222; miR-146b; miR-21; miR-181b) in the plasma of patients with papillary thyroid cancer (PTC), nodular goiter (NG) and healthy controls (HC) and evaluated their diagnostic value for differentiation of PTC from NG and HC. Preoperative PTC plasma miRNA expression (n = 49) was compared with plasma miRNA in the HC group (n = 57) and patients with NG (n = 23). It was demonstrated that miR-221; miR-222; miR-146b; miR-21 and miR-181b were overexpressed in preoperative PTC plasma samples compared to HC (p < 0.0001; p < 0.0001; p < 0.0001; p < 0.0001; p < 0.002; respectively). The upregulation in tumor tissue of these miRNAs was consistent with The Cancer Genome Atlas Thyroid Carcinoma dataset. A significant decrease in miR-21; miR-221; miR-146b and miR-181b expression was observed in the plasma of PTC patients after total thyroidectomy (p = 0.004; p = 0.001; p = 0.03; p = 0.036; respectively). The levels of miR-222 were significantly higher in the preoperative PTC compared to the NG group (p = 0.004). ROC curve (receiver operating characteristic curve) analysis revealed miR-222 as a potential marker in distinguishing PTC from NG (AUC 0.711; p = 0.004). In conclusion; circulating miR-222 profiles might be useful in discriminating PTC from NG.

Clinical Analysis of Preoperative Anti-thyroglobulin Antibody in Papillary Thyroid Cancer Between 2011 and 2015 in Beijing, China: A Retrospective Study.

The anti-thyroglobulin antibody (TgAb) has been suggested to be more common in patients with papillary thyroid cancer (PTC). Here, we performed a retrospective study investigated the correlation between TgAb level and PTC in Chinese patients between 2011 and 2015. Patients with goiter who underwent thyroidectomy and received a confirmed pathological diagnosis were enrolled into the study. Clinical characteristics and preoperative thyroglobulin antibody (TgAb) level data were collected from all enrolled patients. Based on the preoperative TgAb test results, patients were divided into a TgAb negative (TgAb-) group (<60 IU/mL) and a TgAb positive (TgAb+) group (≧60 IU/mL). Of the 4,046 patients, 671 patients were TgAb+ while 3,375 patients were TgAb-. There were 535 (79.7%) patients with PTC in the TgAb+ group, and 2,154 (63.8%) patients with PTC in the TgAb- group. The prevalance of PTC was significantly higher in TgAb+ patients than in TgAb- patients. TgAb+ patients were stratified into four groups based on the TgAb titer. The prevalence of PTC did not increase with TgAb titer. No significant difference in TgAb level was noted in patients with different clinicopathologies, including TNM stage, lymph node metastasis, and multifocal carcinoma. Regression analysis suggested a higher risk of PTC malignancy among TgAb+ patients. Preoperative TgAb level ≥60 IU/mL might be associated with a higher risk of PTC. However, there was no titer-dependent association between elevated TgAb titer and PTC malignancy.

Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer.

BACKGROUND: Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated. METHODS: We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated. RESULTS: The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 µg/mL and 101.5 ng/mL in the benign group and 5.4 µg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively). CONCLUSION: Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.

Serum antithyroglobulin antibody levels are not a good predictive factor on detection of disease activity in patients with papillary thyroid carcinoma.

OBJECTIVE: Thyroglobulin antibodies (TgAb) are detected in thyroid cancer patients up to 25%. We investigated the prognostic value of TgAb positivity in patients with papillary thyroid carcinoma (PTC) after initial therapy. PATIENTS AND METHODS: A database of 109 consecutive patients who underwent total thyroidectomy and therapeutic lateral neck dissection followed by remnant ablation for PTC between January 1989 and December 2014 was reviewed We recorded the patients' all serum Tg and TgAb levels over time to establish changing trends. Patients were classified as either positive or negative according to serum TgAb levels. The recurrence or persistence rates in both groups were compared. RESULTS: Of the 109 patients enrolled 14 patients had TgAb positivity. Thirty-two (29.3%) showed disease recurrence or persistent disease during 101 months of follow-up. Twenty-seven of 95 patients (28.4%) with negative TgAb had persistent or recurrent disease, whereas 5 of 14 patients (35.7%) with positive TgAb had persistence or recurrence (P = 0.57). No significant difference in disease-free survival (115.3 ± 10.8 vs. 224.1 ± 16.6 months, P = 0.78) and overall survival (P = 0.59) was observed between TgAb positive and TgAb negative patients. CONCLUSIONS: TgAb status is not useful as a prognostic and predictive factor for clinical outcomes in patients with PTC in our experience.

Serum Anti-p53 Antibody Can Serve as a Predictive Marker for Histological Grade of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: The aim of the study was to clarify the diagnostic impact of measuring serum anti-p53 antibody (S-p53Ab) in predicting the histological grades of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: We compared the measured values and positive prevalence of S-p53Ab across the different histological grades of 111 resected IPMN cases. We also evaluated the TP53 alterations using immunohistochemistry and next-generation sequencing. RESULTS: Serum anti-p53 antibody were detected in 6 of 111 cases, all of their histological grades were high-grade dysplasia (HGD) and invasive carcinoma (INV). Positive prevalence of S-p53Ab was higher in cases with INV (4/35 cases, 11.4%) than those with HGD (2/38 cases, 5.3%), whereas S-p53Abs were undetectable in cases with low-grade dysplasia. Measured S-p53Ab values were not correlated with either carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9). In 4 of 6 S-p53Ab-positive cases, the TP53 alterations-somatic pathogenic mutations or aberrant immunoreactivity-were identified in their IPMN lesions. A combination assay of S-p53Ab, CEA, and CA 19-9 revealed a 38.4% sensitivity and 81.6% specificity for predicting HGD/INV. CONCLUSIONS: Serum anti-p53 antibody can serve as a surrogate marker for TP53 alterations and help predict the presence of HGD/INV in cases with IPMN, in combination with CEA and CA 19-9.

Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs: A case report.

BACKGROUND: Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct (IPNB), distant metastasis remains unexplained especially in cases of carcinoma in situ. In the present study, we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain. CASE SUMMARY: A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma. Laboratory tests on admission reported a mild elevation of alkaline phosphatase, γ-glutamyl transpeptidase, and total bilirubin in serum. Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct (CBD) extending to the left hepatic duct. Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern. Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis. Therefore, a diagnosis of IPNB cT1N0M0 was established. Left hepatectomy with bile duct reconstruction was performed. Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement. The patient was monitored carefully by regular examinations. However, at 32 mo after the operation, a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level. Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated. In addition to histopathological results, a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer. CONCLUSION: This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

Altered Serum MicroRNA Profile May Serve as an Auxiliary Tool for Discriminating Aggressive Thyroid Carcinoma from Nonaggressive Thyroid Cancer and Benign Thyroid Nodules.

Thyroid cancers are the most common malignancy of the endocrine system; however, there is no reliable blood biomarkers for thyroid cancer diagnosis and even for aggressive and nonaggressive thyroid cancers as well as benign nodule discrimination. The present study is aimed at evaluating whether circulating microRNA (miRNA) can differentiate aggressive and nonaggressive thyroid cancer from benign thyroid nodules. In this study, we performed a multiphase, case-control study to screen serum miRNA expression profile in 100 patients with papillary thyroid cancer (PTC), 15 patients with aggressive medullary thyroid carcinoma (MTC), 91 patients with benign nodules, and 89 healthy controls using TaqMan low-density array followed by extensive reverse transcription quantitative real-time PCR validation. The results showed that the serum levels of miR-222-3p, miR-17-5p, and miR-451a were markedly increased, while miR-146a-5p, miR-132-3p, and miR-183-3p were significantly decreased in the PTC and benign nodule groups compared with the control group. There was no difference in the miRNA expression profile between the PTC group and the benign nodule group. Nevertheless, the serum levels of miR-222-3p and miR-17-5p were significantly increased in the MTC group than the benign nodule and control group. Moreover, receiver operating characteristic curve analyses demonstrated that the 2 miRNAs and their panel can accurately discriminate MTC from the benign nodule group and healthy controls. These findings indicated that the altered circulating miRNAs may discriminate PTC and benign thyroid nodules from controls, and serum miR-222-3p and miR-17-5p have the potential to serve as auxiliary tools for diagnosing more aggressive thyroid carcinomas, such as MTC.