RESUMO
Pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AAC) are lethal malignancies with modest benefits from surgery. SOX2 and STIM1 have been linked to anticancer activity in several human malignancies. This study included 94 tumor cases: 48 primary PDAC, 25 metastatic PDAC, and 21 primary AAC with corresponding non-tumor tissue. All cases were immunohistochemically stained for STIM1 and SOX2 and results were correlated with clinicopathologic data, patient survival, and BCL2 immunostaining results. Results revealed that STIM1 and SOX2 epithelial/stromal expressions were significantly higher in PDAC and AAC in comparison to the control groups. STIM1 and SOX2 expressions were positively correlated in the primary and metastatic PDAC (P = 0.016 and, P = 0.001, respectively). However, their expressions were not significantly associated with BCL2 expression. SOX2 epithelial/stromal expressions were positively correlated with the large tumor size in the primary AAC group (P = 0.052, P = 0.044, respectively). STIM1 stromal and SOX2 epithelial over-expressions had a bad prognostic impact on the overall survival of AAC (P = 0.002 and P = 0.001, respectively). Therefore, STIM1 and SOX2 co-expression in tumor cells and intra-tumoral stroma could contribute to the development of PDAC and AAC. STIM1/SOX2 expression is linked to a bad prognosis in AAC.
Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Ampola Hepatopancreática/patologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Prognóstico , Adenocarcinoma/patologia , Células Estromais/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição SOXB1/metabolismoRESUMO
BACKGROUND: Now, targeted therapy and immunotherapy are promoted. tumour -Associated Macrophages (TAMs) are an essential component of immune-response in breast cancer(BC) with prognostic controversy. Additionally, their recruiting factors are still obscure. Purpose:This study aimed to evaluate the prognostic significance of CD163 and CD47 in BC of No Special Type (BC-NST) and to explore their suggested role in recruiting TAMs. MATERIAL AND METHODS: This immunohistochemical study was conducted on 91 archival specimens of breast cases. Immunoreactivity scores were correlated with TAMs density, clinicopathological data, and survival. RESULTS: Revealed the highest CD163 expression was detected in the pure DCIS group (p = 0.016), while the highest CD47 expression and high TAMs density were reported in the invasive group (p = 0.008, and p = 0.002 respectively) followed by the DCIS group. In IC-NSTs the CD163 and CD47 scores were associated with poor prognostic parameters like(high grade, advanced stage, distant metastasis, ER negativity,Ki67 index, post-surgical chemotherapy, poor NPI group, high mitotic count, dense infiltration of TAMs, shorter OS). Also, CD47 was associated with the dens infiltration of TAMs in DCIS (p = 0.001). There was a significant correlation between tumour cell expression of CD163 and CD47 in IC-NSTs and DCIS (p = 0.002 and p = 0.009 respectively). CONCLUSIONS: High CD163 and CD47 expressions in both DCIS andIBC are intimately associated, significantly associated with poor prognosis and are important provoking factors of TAMs.
Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Neoplasias da Mama , Antígeno CD47 , Imuno-Histoquímica , Receptores de Superfície Celular , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Diferenciação Mielomonocítica/imunologia , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Antígenos CD/metabolismo , Feminino , Antígeno CD47/metabolismo , Antígeno CD47/imunologia , Microambiente Tumoral/imunologia , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/análise , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Pessoa de Meia-Idade , Prognóstico , Adulto , IdosoRESUMO
BACKGROUND: Despite recent advances in therapy modalities of colorectal cancer (CRC), it is still the third cause of cancer-related deaths worldwide. Thus, the search for new target therapies became mandatory. DDR1 is a collagen receptor that has a suggested role in cellular proliferation, tumor invasion, and metastasis. MATERIAL AND METHODS: Forty-eight cases of CRC, 20 of CR adenoma, and 8 cases of non-tumoral colonic tissue were subjected to immunohistochemistry by DDR1 and ß-catenin antibodies. Results were compared among the different studied groups and correlated with clinicopathologic data and available survival data. Also, the expression of both proteins was compared versus each other. Results were compared among the 3 studied groups and correlated with clinicopathologic and survival data. RESULTS: It revealed a stepwise increase of DDR1 expression among studied groups toward carcinoma (P = 0.006). DDR1 expression showed a direct association with stage D in the modified Dukes' staging system (P = 0.013), higher-grade histologic types (P = 0.008), and lymph node invasion (P = 0.028) but inverse correlation with the presence of intratumoral inflammatory response (TIR) (P = 0.001). The shortest OS was associated with strong intensity of DDR1 (P = 0.012). The DDR1 and ß-catenin expressions were significantly correlated (P = 0.028), and the combined expression of both was correlated with TNM staging (P = 0.017). CONCLUSION: DDR1 overexpression is a frequent feature in CRC and CR adenoma. DDR1 is a poor prognostic factor and a suppressor of the TIR. DDR1 and ß-catenin seem to have a synergistic action.
Assuntos
Adenoma , Carcinoma , Neoplasias Colorretais , Humanos , beta Catenina , Neoplasias Colorretais/patologia , Relevância Clínica , Prognóstico , Receptor com Domínio Discoidina 1RESUMO
Diagnosis of Prostatic adenocarcinoma (PAC) is still a problematic issue. The objective of this study was to evaluate the diagnostic and prognostic value of ERG immunohistochemical (IHC) expression compared to MAGI2. MATERIALS AND METHODS: This study was conducted on 56 cases of PAC and 29 cases of nodular prostatic hyperplasia (NPH). IHC staining for ERG and MAGI2 was applied to archival formalin-fixed paraffin-embedded blocks. Semi-quantitative scoring was compared and correlated with clinicopathologic parameters and the Ki-67 index. RESULTS: Revealed positive ERG in 51.8% of PAC while all NPH cases were negative. On the other hand, MAGI2 was detected in 91.1% of PAC versus 17.2% of NPH. Using ROC curve, the ERG showed 53.6% sensitivity, 100% specificity, 76.5% diagnostic accuracy (DA) and area under the ROC curve 0.768 in comparison to MAGI2 that showed (91.1%, 86.2%, 88.25% and 0.948 respectively). Analysis of the combined use of the two markers revealed 95% sensitivity, 100% specificity, and 94% DA when tested synchronously. Moreover, a statistically significant inverse relationship could be detected between ERG expression and the Gleason grading group (P = 0.01) and Ki-67 index (P < 0.001). In addition, high-grade prostatic intraepithelial neoplasia (HGPIN) adjacent to carcinoma; showed positive expressions in (1/11 cases, 9.11%) for ERG and (6/11 cases, 54%) for MAGI2. CONCLUSION: This study recommends using both ERG and MAGI2 in a cocktail for better diagnostic validity of PAC. Only ERG expression could be a good prognostic indicator.
Assuntos
Carcinoma/diagnóstico , Carcinoma/metabolismo , Próstata/patologia , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasias da Próstata/patologia , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Idoso de 80 Anos ou mais , Egito/epidemiologia , Guanilato Quinases , Humanos , Imuno-Histoquímica/métodos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Valor Preditivo dos Testes , Prognóstico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasia Prostática Intraepitelial/diagnóstico , Neoplasia Prostática Intraepitelial/patologia , Sensibilidade e Especificidade , Regulador Transcricional ERGRESUMO
This study aims to investigate the expression of SIX1, EYA2, and E-cadherin in ovarian cancer (OC). It was conducted on 97 cases of surface epithelial tumors (SEOTs). Immunohistochemistry (IHC) staining for the three markers was applied to archival paraffin-embedded sections. Results of semi-quantitative scoring were statistically compared, correlated with clinic-pathologic parameters, response to therapy and with patient survival. RESULTS: There was a significant association of SIX1 expression in the intratumoral stroma (ITS) with malignant cases (P < 0.0001). There was a significant direct correlation between tumour cell expression of SIX1 and EYA2 (P = 0.03) and an inverse correlation between SIX1 and E-cadherin (P = 0.03). Additionally, there were direct correlations between SIX1 expression and larger tumour size (P = 0.05), high mitosis (P < 0.0001), and advanced FIGO stage (P = 0.06), and between EYA2 expression and LN metastasis (P = 0.02), and low apoptotic index (P = 0.007). Only SIX1 expression in ITS affected the patient survival by univariate analysis (P = 0.004). CONCLUSIONS: SIX1/EYA2 complex may have a poor prognostic role in OC. SIX1 expression in ITS may be used as a predictive marker of stromal invasion in ovarian borderline tumors and could affect patients' survival in OC. SIX1, EYA2, and E-cadherin may constitute a pathway that could be targeted to stop the progression of SEOTs.
Assuntos
Caderinas , Carcinoma Epitelial do Ovário , Proteínas de Homeodomínio , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Nucleares , Proteínas Tirosina Fosfatases , Adulto , Idoso , Idoso de 80 Anos ou mais , Caderinas/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Transição Epitelial-Mesenquimal , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Proteínas Tirosina Fosfatases/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
Toxoplasma gondii is the causative parasite of an important worldwide disease. This obligate intracellular parasite can infect and replicate inside any nucleated cells including those of pancreas. Insulin is a hormone secreted by the pancreas and is responsible for controlling blood glucose concentration. Deficiency of insulin production accounts for the occurrence of type-1 diabetes mellitus (T1D). Thus, theoretically, toxoplasmosis could play a possible role in the development of T1D. However, the studies on this theory are still insufficient; therefore, this work was designed. Interestingly, in the case-control study, seropositivity of anti-Toxoplasma IgG was significantly higher among T1D (86.37%) in comparison with T2D (66.67%) and the control group (60%). Moreover, the odd ratio of chronic toxoplasmosis was 4.2 folds higher among T1D patients than among controls. The experimental study included acute and chronic Me49 T. gondii infected mice groups in addition to a control group. Pathological examination revealed the presence of T. gondii zoites adjacent to the islets of Langerhans and in pancreatic parenchyma of acutely infected mice. With chronic infection, there was a significant reduction of islets number and sizes in association with grade-1 insulitis. Additionally, the immunohistochemical study showed significant infiltration of the islets of chronically infected mice by CD8+ and CD45+ immune cells. In contrary to the control group, the islets of the chronic group showed significantly higher expression of the apoptotic marker caspase-3 and a significantly lower expression of the proliferation marker Ki69. Finally, a significant reduction of insulin expression in the islets of chronic infection group was detected in association with a significant increase in serum glucose concentrations; however, the establishment of diabetes did not occur throughout this work. Thus, this study presents an evidence for the probable role of chronic toxoplasmosis in the development of T1D which should be considered in further studies.
Assuntos
Diabetes Mellitus Tipo 1/parasitologia , Ilhotas Pancreáticas/patologia , Toxoplasma/patogenicidade , Toxoplasmose/complicações , Adulto , Animais , Glicemia/análise , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Imuno-Histoquímica , Ilhotas Pancreáticas/parasitologia , Masculino , Camundongos , Organismos Livres de Patógenos EspecíficosRESUMO
Background & Objective: Prostatic adenocarcinoma (PAC) is the second most prevalent cancer and the fifth leading cause of cancer death in men worldwide. Additionally, pathologists may face problems diagnosing it reliably and may need more than one marker. Thus, the search for new immunohistochemical biomarkers becomes mandatory. This study aims to investigate P4HB and SOX4 expression in prostatic carcinoma, their possible roles, and clinical significance. Methods: This retrospective study included fifty-six cases of PAC and an equal number of nodular prostatic hyperplasia (NPH) that were immunohistochemically stained by P4HB and SOX4. The results of expression were compared between PAC and NPH cases, followed by correlations with available clinicopathological parameters. Results: There was a highly significant difference between PAC and NPH regarding P4HB and SOX4 expressions in favor of PAC (both P<0.001). ROC curve analysis of the diagnostic power of P4HB showed 79% sensitivity, 76% specificity, and an area under the ROC curve of 0.845, while SOX4 showed (89%, 100%, and 0.946, respectively). P4HB and SOX4 expression showed a direct correlation (P<0.001). Moreover, the H-score of SOX4 expression showed a significant inverse relation with ERG expression (P=0.047). There was a significant correlation between P4HB and SOX4 and Gleason score (P<0.001). Moreover, P4HB expression was significantly associated with lymphovascular invasion (P=0.013), while SOX4 expression showed a significant association with perineural invasion (P=0.05). Conclusion: SOX4 and P4HB seem to have diagnostic and prognostic value in PAC. While there was a direct correlation between SOX4 and P4HB, an inverse relationship between SOX4 and ERG was detected.
RESUMO
BACKGROUND: Globally Renal Cell Carcinoma (RCC) represents 3% of malignant tumours in adults and 1.78% in Egypt. AMPK-related protein kinase 5 (ARK5) is mainly associated with a hypoxic microenvironment which is a feature of the major RCC subtypes. Additionally, it displays decreased mitochondrial respiration. SIRT3 is a mitochondrial deacetylase that modifies multiple mitochondrial proteins. MATERIAL AND METHODS: Fifty eight cases of RCC, and 30 non-neoplastic cases (of End-Stage Kidney Disease (ESKD) were subjected to immunohistochemistry by ARK5 and SIRT3. The results of IHC were correlated together and correlated with the available clinicopathologic and survival data. RESULTS: Although no significant difference was detected between RCC and ESKD groups regarding ARK5 expression, there was a significant association with RCC regarding H-score and nucleocytoplasmic expression (both P = 0.001). Also, SIRT3 was highly expressed in RCC in comparison to the ESKD group (H-score: P = 0.001). There were significant associations between nucleocytoplasmic ARK5 expression and higher tumour grade, low apoptotic and high mitotic indices, tumour extent, advanced tumour stage, and impaired response of tumours to chemotherapeutic drugs (P = 0.039, P = 0.001, P = 0.027, P = 0.011, P = 0.009, and P = 0.014 respectively). Moreover, the H score of ARK5 expression showed significant associations with tumour grade, apoptotic and mitotic indices, tumour extension, tumour stage, and response to therapy (P = 0.01, 0.035, 0.001, 0.004. 0.003 and 0.013). Regarding SIRT3 expression, it showed significant associations with apoptotic and mitotic indices, tumour extent, tumour stage and response to therapy (P = 0.022, 0.02, 0.042, 0.039 and 0.027). Interestingly, there was a highly significant correlation between the expression of ARK5 and SIRT3 (P = 0.009). Univariate survival analysis revealed a significant association between short survival duration and both nucleocytoplasmic expression of ARK5 and positive SIRT3 expression (P = 0.014 and 0.035). CONCLUSION: ARK5 and SIRT3 are overexpressed in RCC and associated with parameters of poor prognosis as well as short survival. Both seem to influence response to therapy in RCC. So, they could be new targets for therapy that may improve tumour response and patients' survival. There is a postulated relationship that needs more extensive investigation.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Sirtuína 3 , Adulto , Humanos , Carcinoma de Células Renais/patologia , Relevância Clínica , Neoplasias Renais/patologia , Prognóstico , Proteínas Quinases , Microambiente TumoralAssuntos
Lentigo/patologia , Neurofibromatoses/patologia , Adolescente , Biópsia por Agulha , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Hiperpigmentação/diagnóstico , Hiperpigmentação/etiologia , Imuno-Histoquímica , Lentigo/diagnóstico , Neurofibromatoses/diagnóstico , Medição de Risco , Estudos de Amostragem , Adulto JovemRESUMO
BACKGROUND: B-cell chronic lymphocytic leukemia/ small lymphocytic lymphoma (B-CLL/SLL) and mantle cell lymphoma (MCL) show many overlapping morphologic and immunophenotyping features, however they have great difference in therapeutic regimens and prognosis. THE AIM OF THE STUDY: Is to determine the diagnostic and prognostic role of clinico-pathologic variables, CD23 and Cyclin D1 oncoprotiens in B-SLL/CLL and MCL. PATIENTS AND METHODS: This study included 25 BCLL/ SLL cases and 25 MCL cases. All cases were carefully examined and stained using CD23 and Cyclin D1 immunostaining. RESULTS: There was significant difference between BCLL/ SLL and MCL regarding several items including pattern of growth, where interfollicular pattern was restricted to B-SLL/CLL while nodular and mantle zone pattern were confined to MCL; pseudo-follicles were only present in B-CLL/SLL. Transformed cells, plasmacytoid cells, peripheral blood lymphocytosis, significant longer survival and good prognosis were statistically more prominent in favor of B-CLL/SLL. On the other hand, cell cleavage, epithelioid histiocytes, plasma cells, naked nuclei, hyalinized venules, deposited hyaline material in background and reticular fibers in addition to higher mitotic index per 20 HPF were more significantly identified in favor of MCL. CD23 was expressed as membranous pattern in 16/25 (64%) of B-CLL/SLL cases and 1/25 (4%) of MCL cases. On the other hand, Cyclin D1 was expressed as nuclear staining in 18/25 (72%) of MCL cases and only 1/25 (4%) of B-CLL/SLL cases. Regarding B-CLL/SLL, age >60 years and mitosis >or=10/20 HPF were independent prognostic factors of shorter survival by multivariate analysis. In MCL, Cyclin D1 overexpression and splenomegaly were independent prognostic factors of survival by multivariate analysis. CONCLUSION: Cyclin D1 is not only implicated in tumor genesis of MCL, but also in progression and extension of the disease when expressed in high levels (50% cut off value) and it seems to have prognostic impact in MCL. This can be used as a basis for future therapeutic strategies targeting cell cycle regulators. This study could support the concept that Cyclin D1 and CD23 immunostaining may be reliable diagnostic tools for discrimination between B-CLL/SLL and MCL.