Predictive value of serum HIF-1α/HIF-2α and YKL-40 levels for vascular invasion and prognosis of follicular thyroid cancer.

OBJECTIVE: This study investigated the significance of serum hypoxia-inducible factor (HIF)-1α/HIF-2 α and Chitinase 3-Like protein 1 (YKL-40) levels in the assessment of vascular invasion and prognostic outcomes in patients with Follicular Thyroid Cancer (FTC). METHODS: This prospective study comprised 83 patients diagnosed with FTC, who were subsequently categorized into a recurrence group (17 cases) and a non-recurrence group (66 cases). The pathological features of tumor vascular invasion were classified. Serum HIF-1α/HIF-2α and YKL-40 were quantified using a dual antibody sandwich enzyme-linked immunosorbent assay, while serum Thyroglobulin (Tg) levels were measured using an electrochemiluminescence immunoassay method. The Spearman test was employed to assess the correlation between serum factors, and the predictive value of diagnostic factors was determined using receiver operating characteristic curve analysis. A Cox proportional hazards regression model was utilized to analyze independent factors influencing prognosis. RESULTS: Serum HIF-1α, HIF-2α, YKL-40, and Tg were elevated in patients exhibiting higher vascular invasion. A significant positive correlation was observed between Tg and HIF-1α, as well as between HIF-1α and YKL-40. The cut-off values for HIF-1α and YKL-40 in predicting recurrence were 48.25 pg/mL and 60.15 ng/mL, respectively. Patients exceeding these cut-off values experienced a lower recurrence-free survival rate. Furthermore, serum levels surpassing the cut-off value, in conjunction with vascular invasion (v2+), were identified as independent risk factors for recurrence in patients with FTC. CONCLUSION: Serum HIF-1α/HIF-2α and YKL-40 levels correlate with vascular invasion in FTC, and the combination of HIF-1α and YKL-40 predicts recurrence in patients with FTC.

Cd34 Immunostaining Adds Specificity To Microvascular invasion Analysis in Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma is the most common primary neoplasia of the liver. Microvascular invasion predicts outcome and defines tumor staging. However, its diagnosis is still a challenge. The present study aims to evaluate inter and intraobserver agreement in identifying the presence of microvascular invasion using conventional and immunohistochemistry histology. Methods: Three pathologists performed the analysis of 76 hepatocellular carcinoma explants to characterize the presence of microvascular invasion using the hematoxylin/eosin stain and immunohistochemistry for CD34. The evaluations were made individually, in two distinct moments. Results were analyzed by the Kappa's coefficient and ROC curves. Results: Our study demonstrated similar agreement for microvascular invasion between hematoxylin/eosin and CD34 methods. However, the intraobserver agreement values for both methods were higher than the interobserver ones. The accuracy of CD34 in relation to hematoxylin/eosin by ROC curves in intraobserver analysis tends to a high specificity, ranging from 82.1 to almost 100%, with sensitivity of 46.9% to 81.1%. In interobserver analysis, CD34 also has a high specificity (84.3% to 85.5%) while its sensitivity is a little shorter (81.2% to 84.3%). Conclusion: Intraobserver higher agreement allows us to suppose that pathologists employed own criteria to evaluate vascular invasion, reinforcing the need of standardization. ROC Curves analysis showed that the CD34 method is more specific than sensitive. Therefore, immunohistochemistry for CD34 should not be used routinely, but it could be useful to help confirming invasion previously seen by conventional histology.

The value of preoperative systemic immune-inflammation index in predicting vascular invasion of hepatocellular carcinoma: a meta-analysis

Vascular invasion and systemic immune-inflammation index (SII) are risk factors for the prognosis of patients with hepatocellular carcinoma. At present, the correlation between the two is not clear. This meta-analysis explored the relationship between preoperative SII and vascular invasion in patients with hepatocellular carcinoma. According to the search formula, the Pubmed, Embase, Cochrane, Web of Science, and CNKI databases were searched for the relevant research until March 2020. After the quality evaluation of the included literature, the odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as the effect measure. Stata 15. 0 software was used for statistical analysis. The meta-analysis eventually included seven retrospective cohort studies of 3583 patients with hepatocellular carcinoma. The results showed that the choice of SII cut-off value affects SII's efficiency in predicting the risk of vascular invasion. In the cohort of studies with appropriate SII cut-off value, the high SII preoperative group had a higher risk of vascular invasion (OR=2.62; 95%CI: 2.07-3.32; P=0.000) and microvascular invasion (OR=1.82; 95%CI: 1.01-3.25; P=0.045) than the low SII group. The tumor diameter (OR=2.88; 95%CI: 1.73-4. 80; P=0.000) of the high SII group was larger than that of the low SII group. There was no publication bias in this study (Begg's test, P=0.368). As a routine, cheap, and easily available index, SII can provide a certain reference value for clinicians to evaluate vascular invasion before operation.

Prognostic importance of the lymphovascular invasion in head and neck adenoid cystic carcinoma: A systematic review and meta-analysis.

The presence of lymphovascular invasion is considered a prognostic determinant for different human neoplasms and is frequently taken into account by surgeons and oncologists to determine patients' treatment. However, the exact frequency of this microscopic event and its prognostic impact for patients affected by adenoid cystic carcinoma (AdCC) remains unclear. Therefore, the aim of this study was to carry out a systematic review and meta-analysis to address the prevalence and the prognostic potential of lymphovascular invasion in head and neck AdCC. A literature search on PubMed, Scopus, ClinicalTrials.gov, Web of Science and ProQuest databases was undertaken in January 2019. The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS). The relative frequency of lymphovascular invasion and its possible association with other clinicopathological parameters were addressed. A total of 22 studies and 2117 patients were included in this study. The frequency of lymphovascular invasion ranged from 5.2% to 72.5%. Lymphovascular invasion was associated with an increased likelihood of lymph node metastasis (OR = 2.58; 95% CI 1.61-4.12; p = 0.0001) and death (OR = 3.09; 95% CI 1.82-5.26; p = 0.0001), solid/higher-grade AdCC were more likely to present lymphovascular invasion (OR = 5.51; 95% CI 1.87-16-21; p = 0.002) and patients with this microscopic finding had a significantly lower OS (HR = 8.30; 95% CI 1.68-40.91; p = 0.009) and DFS (HR = 3.76; 95% CI 1.13-12.53; p = 0.03). In conclusion, lymphovascular invasion seems to be a significant predictor of poor prognosis for head and neck AdCC patients.

Predictive factors for central lymph node and lateral cervical lymph node metastases in papillary thyroid carcinoma.

BACKGROUND: Central lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is common. But the association between primary tumor characteristics and specific features of metastatic lymph nodes in PTC has not been fully identified. Determining risk factors for LNM may help surgeons determine rational extent of lymph node dissection. METHODS: Data from 432 patients who underwent thyroidectomy with cervical lymph node dissection for PTC were retrospectively analyzed. The relationships between LNM to central compartment or lateral compartment and clinicopathologic factors were analyzed. Cox regression model was used to determine the risk factors for recurrence-free survival (RFS). RESULTS: Central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) were found in 216 (50.0%) and 65 (15.0%) patients, respectively. In the multivariate analysis for CLNM, patients < 45 years of age (OR 2.037, 95% CI 1.388-2.988, P < 0.001), extrathyroidal invasion (OR: 2.144, 95% CI 0.824-5.457, P = 0.011), vascular invasion (OR 13.817, 95% CI 1.694-112.693, P = 0.014), LLNM (OR 2.851, 95% CI 1.196-6.797, P = 0.014) and TNM Stage III-IV (OR 465.307, 95% CI 113.903-1900.826, P < 0.001) were independent predictors for high prevalence of CLNM. In the multivariate analysis for LLNM, tumor size more than 1cm (OR 3.474, 95% CI 1.728-6.985, P < 0.001) and CLNM (OR 5.532, 95% CI 2.679-11.425, P < 0.001) were independent predictors for high prevalence of LLNM. Moreover, tumor with T3-T4 stage, extrathyroidal invasion and CLNM were the significant factors related to the RFS. CONCLUSION: For patients with pre-operative risk factors of LNM, an accurate preoperative evaluation of central compartment or lateral compartment is needed to find suspicious lymph nodes. And prophylactic lymph node dissection should be performed in patients with high risk of CLNM. Moreover, we suggest performing close follow-up for patients with high risk of RFS.

Avaliação imunoistoquímica da via de sinalização Hedgehog no carcinoma hepatocelular e correlação com fatores prognósticos / Immunohistochemical evaluation of the Hedgehog signaling pathway in hepatocellular carcinoma and correlation with prognostic factors

Introdução: o carcinoma hepatocelular (CHC) é a neoplasia maligna primária mais comum no fígado, e apresenta aumento de sua incidência e mortalidade com o avançar da idade. Esta neoplasia encontra-se intimamente associada à cirrose hepática como doença de base, que por sua vez têm como etiologia principal as infecções virais crônicas, como os vírus da hepatite B (HBV) e da hepatite C (VHC), responsáveis por aproximadamente 85% dos casos, além de injúrias hepáticas causadas por álcool e por esteato-hepatite não alcoólica. Além das várias vias de sinalização já descritas na hepatocarcinogênese, a via do Hedgehog pode ser destacada, já que desempenha importante papel na proliferação e diferenciação celulares durante o período embrionário. Objetivo: este estudo tem como objetivo avaliar a expressão do fator ligante Sonic Hedgehog (Shh) em amostras de CHC obtidas em amostras de pacientes submetidos a transplante hepático no Hospital das Clínicas da Universidade Federal de Minas Gerais (HC- UFMG) e correlacionar os índices de marcação com fatores prognósticos clínicos e morfológicos. Metodologia: foi realizada avaliação imunoistoquímica da expressão do ligante Shh em 36 amostras de CHC arquivadas no departamento de anatomia patológica do HC- UFMG, bem como expressão no parênquima cirrótico adjacente. Os dados clínicos e morfológicos de todos os casos foram obtidos através de revisão dos prontuários, bem como das lâminas originais e laudos histopatológicos, arquivados no banco de dados do HC-UFMG. Foi então realizada correlação da expressão do Shh com o escore MELD, níveis séricos de alfa- fetoproteína, grau de diferenciação tumoral, presença ou ausência de invasão angiolinfática, número de nódulos tumorais identificados, tamanho do maior nódulo e etiologia da doença cirrose concomitante. Resultados: através de correlação entre variáveis dicotômicas pelo teste do qui-quadrado, dois fatores morfológicos identificados no exame convencional de HE (grau de diferenciação tumoral e invasão vascular) mostraram correlação direta com a intensidade de expressão citoplasmática da proteína Shh (p = 0,014 e p = 0,003, respectivamente). As demais variáveis não mostraram correlação estatisticamente significante com a expressão tumoral ou parenquimatosa do Shh (p > 0,05). Discussão: a correlação direta entre o grau de diferenciação tumoral e a presença de invasão vascular com a expressão citoplasmática forte do Shh permite inferir que esta marcação é mais evidente em tumores com maior potencial de agressividade, já que esses parâmetros morfológicos são considerados fundamentais para estabelecimento prognóstico. Conclusão: a expressão citoplasmática forte da proteína Shh no carcinoma hepatocelular pode ser considerada como um fator associado a pior prognóstico do CHC. A VIIidentificação dessa expressão estimula o desenvolvimento de estudos que considerem a utilização de quimioterápicos inibidores via Hedgehog para o tratamento clínico do CHC.

Introduction: hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm in the liver, with an increase in its incidence and mortality with advancing age. This neoplasm is closely associated with hepatic cirrhosis as the underlying disease, which has its main etiology in chronic viral infections, such as hepatitis B virus (HBV) and hepatitis C virus (HCV), responsible for approximately 85% of cases, in addition to liver injury caused by alcohol. In addition to the various signaling pathways already described in hepatocarcinogenesis, the Hedgehog pathway can be highlighted, since it plays an important role in cell proliferation and differentiation during the embryonic period. Objective: this study aims to evaluate the expression of binding protein Sonic Hedgehog (Shh) in HCC samples obtained from patients submitted to liver transplantation at the Clinical Hospital of the Federal University of Minas Gerais (HC-UFMG) and to correlate its marking indices with clinical and morphological prognostic factors. Methodology: immunohistochemical evaluation of Shh binding protein expression was performed in 36 CHC samples stored in the HC-UFMG pathology department, as well as expression in the adjacent cirrhotic parenchyma. The clinical and morphological data of all the cases were obtained through a review of the medical records, as well as review of original slides and histopathological reports, filed in the HC-UFMG database. Correlation of Shh expression with MELD score, alpha-fetoprotein levels, degree of tumor differentiation, presence or absence of angiolymphatic invasion, number of tumor nodules identified, size of largest nodule, and etiology of concomitant cirrhosis disease were performed. Results: two morphological factors identified in conventional HE examination (degree of tumor differentiation and vascular invasion) were directly correlated with the intensity of Shh protein expression (p = 0.014 and p = 0.003, respectively). The other variables did not show a statistically significant correlation with the tumor or parenchymal expression of SHH (p> 0.05). Discussion: the direct correlation between the degree of tumor differentiation and the presence of vascular invasion with the strong cytoplasmic expression of Shh allows us to infer that this expression is more evident in tumors with greater aggressiveness potential, since these morphological parameters are considered fundamental for prognostic establishment. Conclusion: the strong cytoplasmic expression of Shh protein in hepatocellular carcinoma can be considered as a factor associated with worse prognosis. The identification of this expression allow us to study and consider the use of chemotherapeutic agents that act blocking the Hedgehog pathway for the clinical treatment of HCC.

Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma.

Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy.

The role of immunohistochemistry in the detection of vascular invasion in specimens of endoscopic submucosal dissection / O papel da imuno-histoquímica na detecção de invasão vascular em espécimes de dissecção endoscópica da submucosa

INTRODUCTION: Endoscopic submucosal dissection (ESD) of early neoplasias of the gastrointestinal tract (GIT) has been increasingly applied as an alternative to invasive surgical procedures, with the aim to preserve the patient's organ and quality of life, although it does not allow the histopathological analysis of lymph nodes. Previous studies demonstrated that the presence of neoplastic emboli in lymphatic (lymphatic vascular invasion [LVI]) or blood vessels (blood vascular invasion [BVI]) is considered a positive predictive factor for the occurrence of lymph node metastasis. The assessment of vascular invasion carried out only by routine hematoxylin and eosin staining (HE) may yield both falsepositive and false-negative results. D2-40 is a specific monoclonal antibody to the lymphatic endothelium. Thus, it is useful for identifying LVI and distinguishing if tumor embolization is found in blood or lymphatic vessels. OBJECTIVE: To determine the role of immunohistochemistry (IHC) in the assessment of ESD specimens by comparing the detection of LVI and BVI by HE and IHC with D2-40 and CD34 immunolabeling. METHOD: We conducted the IHC study using D2-40 and CD34 markers (pan-endothelial) in 30 cases of ESD with histological diagnosis of carcinoma in order to assess the presence of LVI and BVI. RESULTS: The detection of LVI was more prevalent than BVI. Three out of six cases with LVI were false-positive by HE and six were false-negative by IHC. Regarding BVI, five cases were identified and one was false-negative by IHC. CONCLUSION: Our results indicated that the histopathological analysis of ESD specimens by exclusively routine HE staining does not allow proper evaluation of BVI or LVI.

INTRODUÇÃO: A dissecção endoscópica da submucosa (DES) de neoplasias precoces do trato gastrointestinal (TGI) tem sido cada vez mais aplicada como alternativa aos procedimentos cirúrgicos invasivos, visando a preservar o órgão e a qualidade de vida do paciente, contudo, não possibilita a avaliação histopatológica de linfonodos. Estudos anteriores demonstraram que a presença de êmbolos neoplásicos, em vasos linfáticos (invasão vascular linfática [IVL]) ou sanguíneos (invasão vascular sanguínea [IVS]), é considerada um fator preditivo positivo para ocorrência de metástase linfonodal. A avaliação da invasão vascular realizada apenas pela coloração de rotina hematoxilina e eosina (HE) pode gerar resultados falso-positivos e falso-negativos. O D2-40 é um anticorpo monoclonal específico para endotélio linfático, sendo, portanto, útil para identificar IVL e distinguir se a embolização tumoral encontra-se em vasos sanguíneos ou linfáticos. OBJETIVO: Determinar o papel do estudo imuno-histoquímico (IHQ) na avaliação de espécimes de DES, comparando a detecção de IVL e IVS, pelo HE e IHQ com marcação por D2-40 e CD34. MÉTODO: Foi realizado estudo IHQ utilizando os marcadores D2-40 e CD34 (pan-endotelial) em 30 casos de produtos de DES com diagnóstico histológico de carcinoma para avaliar a presença de IVL e IVS. RESULTADOS: A detecção de IVL foi maior que a de IVS. Dos seis casos com IVL ao HE, três eram falso-positivos e seis, falso-negativos à IHQ. Em relação à IVS, foram identificados cinco casos falsopositivos e um falso-negativo à IHQ. CONCLUSÃO: Nossos resultados indicaram que a análise histopatológica dos produtos de DES realizando apenas a coloração HE não permite a avaliação adequada da presença de IVS ou IVL.