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PURPOSE: Our aim was to assess the ability of simultaneous immunohistochemical staining (IHC) for p16 and p53 to accurately subclassify head and neck squamous cell carcinomas (HNSCC) as HPV-associated (HPV-A) versus HPV-independent (HPV-I) and compare p53 IHC staining patterns to TP53 mutation status, p16 IHC positivity and HPV status. METHODS: We stained 31 HNSCCs for p53 and p16, and performed next-generation sequencing (FoundationOne©CDx) on all cases and HPV in-situ hybridization (ISH) when sufficient tissue was available (n = 23). p53 IHC staining patterns were assessed as wildtype (wt) or abnormal (abn) patterns i.e. overexpression, null or cytoplasmic staining. RESULTS: In a majority of cases (28/31) interpretation of p16 and p53 IHC was straightforward; 10 were considered HPV-A (p16+/p53wt) and 18 cases were HPV-I (p16-/p53abn). In the remaining three tumours the unusual immunophenotype was resolved by molecular testing, specifically (i) subclonal p16 staining and wild type p53 staining in a tumour positive for HPV and with no TP53 mutation (HPV-A), (ii) negative p16 and wild type p53 staining with a TP53 mutation and negative for HPV (HPV-I), and (iii) equivocally increased p16 staining with mutant pattern p53 expression, negative HPV ISH and with a TP53 mutation (HPV-I). CONCLUSION: Performing p16 and p53 IHC staining simultaneously allows classification of most HNSCC as HPV-A (p16 +, p53 wild type (especially basal sparing or null-like HPV associated staining patterns, which were completely specific for HPV-A SCC) or HPV-I (p16 -, p53 mutant pattern expression), with the potential for limiting additional molecular HPV or mutational testing to selected cases only.
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Biomarcadores Tumorais , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias de Cabeça e Pescoço , Imuno-Histoquímica , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína Supressora de Tumor p53 , Humanos , Inibidor p16 de Quinase Dependente de Ciclina/análise , Proteína Supressora de Tumor p53/análise , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Biomarcadores Tumorais/análise , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Masculino , Feminino , Idoso , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Adulto , Idoso de 80 Anos ou maisRESUMO
Background: The association of chronic sclerosing sialadenitis and IgG4-related disease (IgG4-RD) has resulted in the more frequent identification of IgG4-positivity in submandibular gland inflammations, also uncovering IgG4 overexpression in nonspecific inflammations. These findings lead us to hypothesise that IgG4-positive sialadenitis represents a continuous inflammatory process overlapping histologically with IgG4-RD, possibly differing in aetiology. However, the antigen underlying IgG4 overexpression in IgG4-positive sialadenitis and IgG4-RD remains unknown. Materials and methods: Here, we investigated toll-like receptor (TLR) - mediated bacterial inflammation in submandibular gland tissues of patients with IgG4-positive and IgG4-negative chronic inflammatory lesions of the submandibular gland (n = 61), with noninflamed submandibular glands serving as controls (n = 4). Utilising immunohistochemistry, we assessed the expression of TLR2 and TLR4, lipopolysaccharide (LPS) and the P. gingivalis-specific antigen gingipain R1. Results: We observed TLR2- and TLR4-immunopositivity in 64 (98%) samples. However, TLR2 and TLR4 staining intensity was significantly stronger in the IgG4-positive group. LPS- and gingipain R1 immunopositivity were observed in 56 (86%) and 58 (89%) samples, respectively. LPS-positivity localised exclusively in mast cell-like cells, while gingipain R1-positivity remained scarce. Conclusions: A stronger TLR2 or TLR4 expression in IgG4-positive sialadenitis may indicate a tissue-related factor underlying this form of chronic sialadenitis. LPS- and P. gingivalis immunopositivity remained weak throughout this series. Thus, gram-negative bacteria may not represent pathogens underlying these forms of chronic sialadenitis.
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INTRODUCTION: Pancreatic cancer (PC) is associated with a high risk of venous thromboembolic events (VTEs). We investigated the incidence of VTE before and after the diagnosis of PC and its association with overall survival. METHODS: We identified PC patients diagnosed in 2013-2016 from the Finnish Cancer Registry. Data on healthcare visits and death were collected, along with follow-up data through the end of 2020. We compared patients who underwent radical-intent surgery (RIS) to those who underwent palliative treatment (PT) alone. RESULTS: We identified 4086 PC patients, of whom 343 (8.4%) underwent RIS and 3743 (91.6%) received PT. VTE incidence within 1 year before a PC diagnosis was higher in the PT (4.2%, n = 156) than in the RIS group (0.6%, n = 2; p < 0.001). The cumulative incidence of VTE at 12 and 24 months after a PC diagnosis was 6% (n = 21) and 9% (n = 31), respectively, within the RIS group, and 8% (n = 286) and 8% (n = 304) within the PT group. In the PT group, a VTE within 1 year before a PC diagnosis was independently associated with a worse survival {hazard ratio, HR 1.9 [95% confidence interval (CI) 1.6-2.2]}. In both groups, VTE after a PC diagnosis was associated with a worse survival [RIS group: HR 2.6 (95%CI 1.8-3.7) vs. PT group: HR 2.2 (95%CI 1.9-2.4)]. CONCLUSIONS: A VTE within 1 year before a PC diagnosis more often occurred among PT PC patients than among patients who underwent RIS. VTE might serve as a diagnostic clue to detect PC at an earlier stage.
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Neoplasias Pancreáticas , Sistema de Registros , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/etiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/complicações , Masculino , Finlândia/epidemiologia , Feminino , Idoso , Incidência , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Cuidados Paliativos , Fatores de Risco , Estudos de CoortesRESUMO
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and lack of effective diagnostic and prognostic biomarkers. A rich and activated desmoplastic tumor stroma is considered a hallmark of PDAC, and therefore stromal components could be a source of possible new prognostic biomarkers. Expression of collagen VI (COL6) has been found to associate with prognosis in many forms of cancer but has been less extensively studied in PDAC. Some previous studies indicate that COL6 expression is upregulated in PDAC, and it could have prognostic value. METHODS: In this study the expression of COL6 was analyzed by immunohistochemistry in tissue microarrays (TMAs) containing tumor tissue samples from 164 (n = 164) PDAC patients who had undergone surgical resection. Scoring results were combined with clinical data, and the prognostic significance of COL6 was estimated with Kaplan-Meier survival estimates and multivariable Cox regression analysis. COL6 protein expression patterns were further investigated in The Cancer Proteome Atlas (TCPA) dataset (n = 103) and in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset (n = 138). COL6 mRNA expression in PDAC tissue was investigated using The Cancer Genome Atlas (TCGA) by forming a dataset containing gene expression data and corresponding clinical variables of 168 (n = 168) PDAC patients. RESULTS: In this large PDAC TMA cohort we could not find statistically significant (p < 0.05) differences in survival when comparing patients with high and low protein expression of any of the analyzed COL6 α-chains (α1(VI): HR 0.90, 95% CI 0.64-1.28; α2(VI): HR 1.28, 95% CI 0.86-1.89; α3(VI): HR 0.91, 95%CI 0.64-1.29). Similar results were obtained when assessing expression of COL6 in public data from TCPA, CPTAC and TCGA. CONCLUSIONS: In contrast with previous studies and some other cancer forms, we did not find any association of COL6 tissue expression and PDAC survival on protein or mRNA level.
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The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.
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Neoplasias Orofaríngeas , Infecções por Papillomavirus , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Glicoproteínas/metabolismo , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/patologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
PURPOSE: Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL. METHODS: We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma. RESULTS: We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS. CONCLUSION: Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent.
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Herpesviridae , Neoplasias dos Seios Paranasais , Polyomavirus , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/virologia , Idoso , Feminino , Polyomavirus/isolamento & purificação , Polyomavirus/genética , Herpesviridae/isolamento & purificação , Herpesviridae/genética , Adulto , Idoso de 80 Anos ou mais , DNA Viral/análise , Hibridização In SituRESUMO
Background: The etiology behind different types of chronic sialadenitis (CS), some of which exhibit IgG4 overexpression, is unknown. Further, IgG4-related disease (IgG4-RD) commonly affects the submandibular gland, but its relationship to IgG4-overexpressing CS, and the antigen triggering IgG4 overexpression, remain unknown. Materials and Methods: By qPCR, we assessed the presence of 21 DNA-viruses causing IgG4 overexpression in submandibular gland tissue from patients with IgG4-positive and IgG4-negative CS. Healthy submandibular glands and glands with sialolithiasis without CS were used as controls. We examined the distribution of HHV-7, HHV-6B and B19V DNA, within virus PCR-positive tissues with RNAscope in-situ hybridization (RISH). Results: We detected DNA from seven viruses in 48/61 samples. EBV DNA was more prevalent within the IgG4-positive samples (6/29; 21%) than the IgG4-negative ones (1/19; 5.3%). B19V DNA was more prevalent within the IgG4-negative samples (5/19; 26%) than the IgG4-positive ones (4/29; 14%). The differences in virus prevalence were not statistically significant. Of the IgG4-RD samples (n = 3) one contained HHV-6B DNA. RISH only showed signals of HHV-7. Conclusions: None of the studied viruses are implicated as triggering IgG4-overexpression in CS. Although our results do not confirm viral etiology in the examined conditions, they provide valuable information on the prevalence of viruses in both diseased and healthy submandibular gland tissue.
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OBJECTIVES: Adenoid cystic carcinoma (ACC) of the salivary glands has poor long-term prognosis and a high metastatic rate. Toll-like receptors (TLRs), first-line immune activators, have been associated with both tumor progression and suppression. We aimed to study TLR3 and TLR7 behavior in ACC. MATERIALS AND METHODS: We studied TLR3 and TLR7 immunoexpression of 46 minor salivary gland ACCs diagnosed at the Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland over the period 1974-2012. The associations of TLR3 and TLR7 immunoexpression with clinicopathological factors were evaluated by χ2-test and Fisher's exact test. RESULTS: In the majority of samples, both TLR3 and TLR7 were immunoexpressed in cytoplasm. The immunoexpression was heterogeneous between individual tumors. Stronger TLR7 immunoexpression associated with recurrence rate and poorer disease-specific survival (DSS). TLR3 did not associate significantly with survival although we found an inverse correlation between TLR3 and TLR7 immunopositivity. Hence, when TLR3 immunoexpression was negative or mild, TLR7 immunoexpression was moderate to strong, and vice versa. CONCLUSIONS: TLR3 and TLR7 are immunoexpressed in minor salivary gland ACC. TLR7 is potentially an independent prognostic marker for recurrence rate and DSS.
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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs. OBJECTIVE: Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we aimed to identify and characterize embryonic signaling pathways that were reinitiated during tumor formation and expansion. METHODS AND RESULTS: Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells. CONCLUSION: Our findings illustrate that E2F1 and E2F8 transcription factors are expressed in pancreatic progenitor and PDAC cells, where they contribute to tumor cell expansion by regulation of cell proliferation, viability, and cell migration making these genes attractive therapeutic targets and potential prognostic markers for pancreatic cancer.
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Apoptose , Carcinoma Ductal Pancreático , Movimento Celular , Proliferação de Células , Fator de Transcrição E2F1 , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Animais , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sobrevivência Celular/genética , CamundongosRESUMO
Biomarkers are not broadly used in the management of head and neck cancers (HNCs). Biomarkers have been beneficial in the management of other cancers, however, not in HNCs. Therefore, we observed the immunopositivity of a novel biomarker called immunoglobulin superfamily member 3 (IGSF3) in tumor tissues in HPV-related and HPV-unrelated OPSCC. Two patient cohorts (C1 and C2) from separate time periods were available for this study (total N = 282). Both consisted of OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2000-2016. For HPV determination, HPV mRNA in situ hybridization was used. Immunohistochemistry was used to assess IGSF3 immunopositivity in cancer tissues. Overall survival (OS) was used as endpoint in the statistical analysis. In C1, stronger immunopositivity of IGSF3 in tumor-infiltrating lymphocytes (TILs) correlated with favorable OS (p = 0.005). Stronger IGSF3 immunopositivity in tumor cells (TCs) was associated with HPV negativity (p = 0.017). Stronger IGSF3 immunopositivity in TILs correlated with HPV positivity (p < 0.001). Elevated IGSF3 immunopositivity in TILs associates with HPV-related tumors and may signify favorable prognosis. The immunopositivity of IGSF3 differs between HPV-related and HPV-unrelated OPSCC.
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BACKGROUND AND OBJECTIVES: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status. METHODS: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex. RESULTS: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60-75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89-3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67-3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28-2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72-3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05-2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63-3.42, p = 0.005), respectively. CONCLUSION: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.
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Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Humanos , Feminino , Masculino , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Europa (Continente)/epidemiologia , Proteínas Proto-Oncogênicas B-raf/genética , Seguimentos , Proteína 1 Homóloga a MutL/genética , Mutação , Prognóstico , Incidência , Suécia/epidemiologiaRESUMO
The tall cell subtype (TC-PTC) is an aggressive subtype of papillary thyroid carcinoma (PTC). The TC-PTC is defined as a PTC comprising at least 30% epithelial cells that are three times as tall as they are wide. In practice, this definition is difficult to adhere to, resulting in high inter-observer variability. In this multicenter study, we validated a previously trained deep learning (DL)-based algorithm for detection of tall cells on 160 externally collected hematoxylin and eosin (HE)-stained PTC whole-slide images. In a test set of 360 manual annotations of regions of interest from 18 separate tissue sections in the external dataset, the DL-based algorithm detected TCs with a sensitivity of 90.6% and a specificity of 88.5%. The DL algorithm detected non-TC areas with a sensitivity of 81.6% and a specificity of 92.9%. In the validation datasets, 20% and 30% TC thresholds correlated with a significantly shorter relapse-free survival. In conclusion, the DL algorithm detected TCs in unseen, external scanned HE tissue slides with high sensitivity and specificity without any retraining.
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INTRODUCTION: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths. The hippo pathway works as a regulator of organ growth and is often a target for mutations in cancer. Ferm domain containing protein 6 (FRMD6) is an activator of the hippo pathway. This study aimed to explore the role of FRMD6 in CRC and to determine how well it works as a prognostic factor among CRC patients. METHODS: The tumor expression of FRMD6 was evaluated using immunohistochemistry in 538 colorectal patients operated on at Helsinki University Hospital. We assessed FRMD6 expression with clinicopathological parameters and the impact of FRMD6 expression on survival. RESULTS: Patients with a high FRMD6 expression exhibited a better prognosis (univariable hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81), with a 5-year disease-specific survival (DSS) of 66.3%. By contrast, patients with a low FRMD6 expression had a 5-year DSS of 52.8%. A high FRMD6 expression level served as an independent predictor for better survival in the Cox multivariable survival analysis (HR 0.53, 95% CI 0.33-0.86). DISCUSSION: To our knowledge, this is the first study to show that a high FRMD6 expression is an independent marker for a better prognosis in CRC and could help determine the prognosis for CRC patients.
Colorectal cancer is one the most common cancers worldwide affecting millions of individuals annually. To improve patient care, novel biomarkers are needed to individualize patient treatment. We show here that a high FRMD6 expression is an indicator of a favorable prognosis. In the future, FRMD6 might serve as a factor for determining which patients need adjuvant treatment following radical surgery.
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Biomarcadores Tumorais , Neoplasias Colorretais , Humanos , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: The clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC). METHODS: We used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC. RESULTS: Single cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224-3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080-2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216-3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067-2.538, P = 0.024). CONCLUSION: Single cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Prognóstico , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Neoplasias de Cabeça e Pescoço/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: Surveillance following resection with curative intent of pancreatic cancer varies widely, and supporting evidence is limited. Recurrence is although frequent, not at least during the first 2 years. Surveillance may be costly, but evidence on how this influences overall survival is not fully elucidated. METHODS, RESULTS: There are reports implying that signs of biological recurrence (increasing CA 19-9) precede radiologically demonstrated recurrence by months. CONCLUSIONS: The possibility of initiating salvage therapy earlier is discussed, potentially based on improved future biomarker panels.
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Carcinoma Ductal Pancreático , Recidiva Local de Neoplasia , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Recidiva Local de Neoplasia/epidemiologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidadeRESUMO
BACKGROUND: Interrupting chemotherapy may explain the reduced overall survival (OS) in patients with pancreatic cancer (PC) with cholangitis. Endoscopic biliary decompression (BD) with metallic stents results in fewer chemotherapy interruptions and a lower cholangitis rate compared with plastic stents. We aimed to determine the impact of cholangitis, neoadjuvant treatment (NAT) interruptions and biliary stent choice on PC patients' survival. METHODS: We conducted a retrospective analysis of 162 patients with cancer of the head of the pancreas undergoing pancreatoduodenectomy after NAT and BD documenting progression-free survival (PFS) and OS. Data on BD, cholangitis, stent type, surgical radicality, and chemotherapy were collected. Survival was estimated based on the Kaplan-Meier method by using the log-rank test and multivariate Cox regression analysis. RESULTS: Median OS and PFS for patients with cholangitis (n = 33, 20%) were 26 and 8 months (95% confidence interval [CI] 20-32 and 5-10 months), respectively, compared with 36 and 17 months (95% CI 31-41 and 12-21 months; p < 0.001 for OS; p = 0.002 for PFS) for patients without cholangitis. Among patients without NAT interruptions median OS and PFS were 35 and 17 months (95% CI 31-40 and 12-21 months), falling to 26 and 7 months (95% CI 18-30 and 5-10 months) among those who experienced an NAT interruption caused by biliary stent failure (n = 26, 16%) (p = 0.039 for OS; p < 0.001 for PFS). We found no difference in OS or PFS between stent types. CONCLUSIONS: Cholangitis and NAT interruptions reduce OS and PFS among PC patients.
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Colangite , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Intervalo Livre de Progressão , Colangite/etiologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Resultado do Tratamento , Stents/efeitos adversosRESUMO
Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, which raises the intratumoral interstitial pressure leading to vascular collapse and hypoxia, inducing angiogenesis. Vascular growth factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), increase in PDAC. A high VEGF and a high circulating Ang-2 associate with shorter survival in PDAC. In addition to the circulatory Ang-2, PDAC endothelial and epithelial cells express Ang-2. No correlation between tumor epithelial nor endothelial cell Ang-2 expression and survival has been published. We aimed to examine Ang-2 expression and survival. This study comprised PDAC surgical patients at Helsinki University Hospital in 2000-2013. Ang-2 immunohistochemistry staining was completed on 168 PDAC patient samples. Circulating Ang-2 levels were measured using ELISA in the sera of 196 patients. Ang-2 levels were assessed against clinical data and patient outcomes. A low tumor epithelial Ang-2 expression predicted shorter disease-specific survival (DSS) compared with a high expression (p = 0.003). A high serum Ang-2 associated with shorter DSS compared with a low circulating Ang-2 (p = 0.016). Ang-2 seemingly plays a dual role in PDAC survival. Further studies are needed to determine the mechanisms causing tumor cell Ang-2 expression and its positive association with survival.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Angiopoietina-2 , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular , Neoplasias PancreáticasRESUMO
BACKGROUND: The implementation of current treatment modalities and their impact on nationwide gastric cancer outcomes remain poorly understood. Biological differences between females and males could impact survival. We aimed to analyze rates of gastric surgery, chemotherapy, and radiotherapy as well as changes in overall survival among gastric cancer patients diagnosed between 2000-2008 and 2009-2016, respectively, in Finland. MATERIAL AND METHODS: Data on gastric cancer patients were collected from national registries. Cox regression analysis and the Kaplan-Meier method were used to analyze differences in survival. RESULTS: We identified 9223 histologically confirmed gastric cancer patients. The rate of gastric surgery decreased from 44% (n = 2282) to 34% (n = 1368; p < 0.001). The proportion of gastric surgery patients who underwent preoperative oncological treatment increased from 0.5% (n = 12) to 16.2% (n = 222) between the calendar periods (p < 0.001) and stood at 30% in 2016. The median overall survival (OS) improved from 30 months [95% confidence interval (CI) 28-33] to 38 months (95%CI 33-42; p = 0.006) and the period 2009-2016 independently associated with a lower risk of death [hazard ratio (HR) 0.78, 95%CI 0.70-0.87] among patients who underwent gastric surgery. Females exhibited a lower risk of death (HR 0.88, 95%CI 0.81-0.97) among patients who underwent gastric surgery. CONCLUSION: Preoperative oncological treatment was gradually introduced into clinical practice and OS among gastric surgery patients improved. Moreover, female surgical patients exhibited a better survival than male patients.