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1.
Anticancer Res ; 39(11): 6403-6412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704874

RESUMO

BACKGROUND: Cytokines, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) take part in many processes involved in tumor progression and invasion such as degradation of the extracellular matrix, influence on immune cells associated with tumor tissue, and angiogenesis. Thus, the aim of this study was to compare the concentration of plasma levels and tissue expression of macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2 and MMP9, and their tissue inhibitors TIMP1 and TIMP2 in patients with cervical cancer, patients with high-grade cervical intraepithelial dysplasia (CIN3) and patients with ectropion. PATIENTS AND METHODS: Concentration and expression of all tested parameters was measured in serum with enzyme-linked immunosorbent assay (ELISA) and in tissue with immunohistochemistry method. RESULTS: The epithelial expression of M-CSF and TIMP1 in cancer tissue was much stronger as compared to that in ectropion and CIN3. In the case of MMP2, lack of or weak expression in epithelial cells was observed in all tested groups. Our studies showed statistical differences of tested parameters in tissue expression and in plasma concentrations in patients with cervical cancer, patients with CIN3 and patients with ectropion. Moreover, data revealed positive correlation between plasma level and cervical cancer cell expression of VEGF. CONCLUSION: Our findings indicate a potential role of all the proteins tested here in cervical cancer diagnosis, especially VEGF. However, further studies will show whether they play a role in the progression of cancerous changes in epithelial tissue of the cervix.


Assuntos
Fator Estimulador de Colônias de Macrófagos/análise , Metaloproteases/análise , Inibidores Teciduais de Metaloproteinases/análise , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/química , Fator A de Crescimento do Endotélio Vascular/análise , Adenocarcinoma/sangue , Adenocarcinoma/química , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/sangue , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/sangue , Metaloproteases/sangue , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Displasia do Colo do Útero/sangue , Neoplasias do Colo do Útero/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
3.
Am J Surg Pathol ; 43(6): 827-834, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31091204

RESUMO

Anal squamous cell carcinomas (ASCCs) frequently harbor human papillomavirus (HPV), most commonly high-risk (HR-) HPV type 16. While p16 immunohistochemistry (IHC) is typically used as a surrogate for HR-HPV status in the oropharynx and cervix, its overexpression can also occur as a result of oncogenic stress and sometimes prove nonspecific. There have been recent investigations into the use of HPV RNA in situ hybridization (RISH) assays as an alternative method, which have shown robust results for squamous cell carcinomas of the oropharynx and cervix. Our study evaluated HPV RISH and p16 IHC in 50 ASCCs, as well as the clinicopathologic features of ASCC relative to HPV status. We found that HPV RISH and p16 IHC were closely in agreement with 96% concordance. Using the 2 methodologies, 78% of ASCCs were HR-HPV positive, 10% were low-risk HPV positive, and 12% were HPV-negative. None of our cases showed co-infection across HR-HPV and low-risk HPV. ASCCs that were not related to HR-HPV were more likely to have a typical keratinizing morphology (P=0.05) and more likely to involve the perianal area (P=0.006). HPV-negative cases were particularly aggressive with high rates of metastases and patient death within 2 years of diagnosis. Overall, HPV RISH appears to be a reliable methodology for testing, and HPV status may have implications for prognostication of ASCCs.


Assuntos
Neoplasias do Ânus/virologia , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Papillomavirus Humano 16/isolamento & purificação , Imuno-Histoquímica , Hibridização In Situ , Infecções por Papillomavirus/virologia , RNA Viral/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/química , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patologia , Feminino , Interações Hospedeiro-Patógeno , Papillomavirus Humano 16/genética , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/patologia , Valor Preditivo dos Testes , Prognóstico , RNA Viral/genética , Reprodutibilidade dos Testes
5.
Zhonghua Zhong Liu Za Zhi ; 41(2): 107-111, 2019 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-30862139

RESUMO

Objective: To investigate the expressional levels and diagnostic values of miR-18a and miR-21 in esophageal carcinoma. Methods: The expressions of miR-18a and miR-21 in esophageal cancer tissues and adjacent tissues from 45 esophageal cancer patients, peripheral blood from 45 esophageal cancer patients and 50 healthy donors respectively were detected by RT-PCR. The expressions of miR-18a and miR-21 in normal esophageal epithelial cell HET-1A, esophageal cancer cell lines including ECA109, KYSE150 and TE1 were also detected. Chemiluminescence immunoassay was used to quantitatively detect the concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), CYRFA21-1 and TPA (tissue polypeptide antigen) in peripheral blood serum from esophageal cancer patients and healthy controls. Meanwhile, the diagnostic effects of miR-18a and miR-21 on esophageal cancer were compared with those of tumor markers in serum. Results: The expression levels of miR-18a and miR-21 in esophageal cancer cells ECA109, KYSE150 and TE1 were 1.64±0.17, 1.62±0.19, 1.46±0.12 and 20.52±1.48, 6.73±0.73, 1.43±0.19, respectively, higher than those in normal esophageal epithelial cells (both P<0.01). The expressions of miR-18a and miR-21 in esophageal cancer tissues were 32.48±28.62 and 8.67±11.98, respectively, significantly higher than those in adjacent tissues (all P<0.001). The expression levels of miR-18a and miR-21 in peripheral blood of patients with esophageal cancer were 12.66±11.92 and 9.15±8.14, respectively, significantly higher than those in the normal control group (both P<0.001). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-18a and miR-21 for diagnosis of esophageal cancer were 0.948 and 0.913 5, respectively. Compared with traditional esophageal tumor markers, the expressions of miR-18a and miR-21 were more sensitive in the diagnosis of esophageal cancer. The sensitivity and accuracy of the expressions of miR-18a and miR-21 combined with traditional esophageal tumor markers in diagnosis of esophageal cancer can be further improved to 97.8% and 68.4%, respectively. Conclusion: Our study reveals that the expressions of miR-18a and miR-21 play important roles in the diagnosis of esophageal cancer and may be potentially novel biomarkers.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , MicroRNAs/metabolismo , Antígenos de Neoplasias/análise , Área Sob a Curva , Biomarcadores Tumorais , Antígeno Carcinoembrionário/análise , Carcinoma de Células Escamosas/química , Estudos de Casos e Controles , Linhagem Celular Tumoral , Neoplasias Esofágicas/química , Esôfago/química , Esôfago/metabolismo , Humanos , Curva ROC , Serpinas/análise , Antígeno Polipeptídico Tecidual/análise
6.
Am J Clin Pathol ; 151(6): 574-583, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30895287

RESUMO

OBJECTIVES: Perineural invasion (PNI) is an important factor in tumor prognosis. We evaluated p75 nerve growth factor receptor (p75NGFR) as a neuromarker for perineural invasion of squamous cell carcinoma. METHODS: A comparison of H&E, and S100 and p75NGFR immunohistochemical staining methods, using sequential sections from 29 samples, for identification nerve bundles and PNI diagnosis, was carried out. RESULTS: p75NGFR and S100 correctly identified more nerve bundles than H&E. Accuracy of p75NGFR was higher than that of S100, but there was no significant difference from H&E. The accuracy of nerve bundle identification by p75NGFR and S100 showed no significant difference among different histopathologic grades of squamous cell carcinomas. p75NGFR gave mild staining of small vessels, while S100 gave strong staining of smooth muscle and glandular tissue. CONCLUSIONS: p75NGFR specifically stains nerve tissue and is better than S100 and H&E in identifying nerve bundles. p75NGFR is expected to become a new neuromarker.


Assuntos
Carcinoma de Células Escamosas/patologia , Períneo/patologia , Receptor de Fator de Crescimento Neural/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Carcinoma de Células Escamosas/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Tecido Nervoso/química , Proteínas S100/análise
7.
Vet J ; 245: 41-48, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30819424

RESUMO

Cutaneous squamous cell carcinoma (cSCC) represents one of the most common malignant skin tumors in dogs. Research aimed at clarifying how the deregulated activity of signalling pathways contributes to cSCC progression can help to identify molecular suitable targets for the development of novel therapies. The present study describes the immunohistochemical expression pattern of two proteins (pAktSer473 and pS6Ser235/236, the latter combined with Ki-67) involved in the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway in canine specimens of normal epidermis, pre-neoplastic epidermis, and cSCC using tissue microarrays. The results suggest that the PI3K/Akt/mTOR signalling pathway has a low expression in the normal canine epidermis, and that selected molecules involved in this signalling pathway are dysregulated during the canine epidermal carcinogenesis process. These findings provide important evidence that the persistent activation of the PI3K/Akt/mTOR signalling pathway represents one of the key events during cSCC progression in canine patients, pointing to the PI3K/Akt/mTOR pathway as a potential therapeutic target.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Cão/metabolismo , Imuno-Histoquímica/veterinária , Fosfoproteínas/análise , Neoplasias Cutâneas/veterinária , Serina-Treonina Quinases TOR/metabolismo , Animais , Carcinoma de Células Escamosas/química , Cães , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Neoplasias Cutâneas/química
8.
Am J Dermatopathol ; 41(3): 205-210, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30640756

RESUMO

High-risk human papillomavirus (HR-HPV) is known to play an oncogenic role in squamous cell carcinoma (SCC) at certain anatomical sites, namely the uterine cervix, oropharynx, and anogenital skin. However, the association between HR-HPV and nonanogenital cutaneous SCC (CSCC) remains controversial. In this study, we addressed this controversy by performing HR-HPV E6/E7 mRNA in situ hybridization (ISH) on 243 CSCC samples. A cocktail of E6/E7 mRNA ISH probes, recognizing 18 HR-HPV genotypes, was applied to a tissue microarray of paraffin-embedded sections of 154 invasive and 89 in situ CSCC specimens. The anatomical sites of CSCC included the head and neck (n = 100), extremities (n = 100), trunk (n = 25), and anogenitalia (n = 18). We also investigated the correlation between the p16 expression and HR-HPV status by immunohistochemistry. The results of HR-HPV E6/E7 mRNA ISH showed that 5.8% (14/243) of all CSCC samples were positive for HR-HPV, including 66.7% (12/18) of the anogenital and only 0.9% (2/225) of the nonanogenital CSCC samples (P < 0.01). For the detection of diffuse p16 expression by immunohistochemistry, the sensitivity was 100% (14/14 HR-HPV-positive CSCC samples), and the specificity was 72.1% (165/229 HR-HPV-negative specimens). Thus, HR-HPV E6/E7 mRNA was rarely detected in nonanogenital CSCC, making it unlikely that the virus contributes to the pathogenesis of this malignancy. In addition, p16 immunoreactivity has a limited value as a surrogate marker for transcriptionally active HR-HPV in nonanogenital CSCC.


Assuntos
Carcinoma de Células Escamosas/virologia , Hibridização In Situ , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , RNA Mensageiro/genética , RNA Viral/genética , Neoplasias Cutâneas/virologia , Análise Serial de Tecidos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patologia , Transformação Celular Viral , Inibidor p16 de Quinase Dependente de Ciclina/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia
10.
Am J Dermatopathol ; 41(1): 1-6, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608261

RESUMO

TLE1 immunohistochemistry is widely used as a biomarker for synovial sarcoma. Recently, we identified TLE1 expression in a subset of melanomas and noted staining in sebaceous glands and follicular epithelium. TLE1 immunohistochemistry has not been well studied in cutaneous tumors. The aim was to investigate TLE1 expression in sebaceous neoplasms, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) to determine whether the staining patterns may aid in the diagnosis or classification of these neoplasms. TLE1 immunohistochemistry was performed on sebaceous adenoma (n = 26), sebaceoma (n = 10), sebaceous carcinoma (n = 19), BCC (n = 20), and SCC (n = 19). Positivity was defined as dark-brown nuclear staining and graded as 3+ (strong staining of >50% of cells at 4×), 2+ (moderate staining of 10-50% of cells at 4× or >50% of cells staining at 10×), and 1+ (weak staining of <50% of cells at 10×). No staining was scored as 0. A score of 2-3+ was considered positive and 0-1+ negative. Nuclear TLE1 expression was identified in 25/26 (96%) sebaceous adenomas, 8/10 (80%) sebaceomas, and 17/19 (90%) sebaceous carcinomas. TLE1 also labeled 19/20 (95%) BCCs and 12/19 (63%) SCCs. TLE1 immunohistochemistry frequently highlights sebaceous neoplasms, BCC, and SCC with a fairly high sensitivity (63%-96%). Therefore, TLE1 is not a specific biomarker for synovial sarcoma and should be evaluated with caution, particularly in cases in which the differential diagnosis may include other cutaneous tumors. In addition, TLE1 does not seem to be useful in the diagnosis or classification of these neoplasms.


Assuntos
Adenoma/química , Biomarcadores Tumorais/análise , Carcinoma Basocelular/química , Carcinoma de Células Escamosas/química , Proteínas Repressoras/análise , Neoplasias das Glândulas Sebáceas/química , Neoplasias Cutâneas/química , Adenoma/patologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Humanos , Imuno-Histoquímica , Gradação de Tumores , Valor Preditivo dos Testes , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias Cutâneas/patologia
11.
Virchows Arch ; 474(3): 333-339, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30607556

RESUMO

Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Carcinoma de Células Escamosas/patologia , Neoplasias da Bexiga Urinária/secundário , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/química , Carcinoma Lobular/mortalidade , Carcinoma Lobular/terapia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Fatores de Tempo , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia
12.
Zhonghua Bing Li Xue Za Zhi ; 48(2): 127-131, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30695865

RESUMO

Objective: To observe the clinicopathologic features of oropharyngeal squamous cell carcinoma associated with human papilloma virus (OPSCC-HPV) and discuss the role and value of different in situ hybridization (ISH) detection methods for HPV in pathologic diagnosis. Methods: Fifteen cases of OPSCC-HPV were collected from Department of Pathology, Beijing Tongren Hospital, Capital Medical University from January 2016 to August 2018. These cases were diagnosed in accordance with the WHO classification of head and neck tumors. The histopathologic features and the clinicopathologic data were retrospectively analyzed. Immunohistochemistry (two-step EnVision method) was done to evaluate the expression of p16, Ki-67 and p53. ISH was used to detect HPV DNA (6/11 and 16/18). RNAscope technology was used to evaluate the presence of HPV mRNAs (16 and 18). Results: The mean age for the 15 patients (8 males, 7 females) was 47 years (range from 30 to 69 years). OPSCC-HPV typically presentedat an advanced clinical stage, six patients had cervical lymphadenopathy (large and cystic), seven had tonsillar swelling, one had tumor at base of tongue, and one had odynophagia. Microscopically the tumors exhibited distinctive non-keratinizing squamous cell carcinoma morphology. Cervical nodal metastases were large and cystic, with thickening of lymph node capsules. OPSCC-HPV raised from crypt epithelium and extended beneath the tonsillar surface epithelial lining as nests and lobules, often with central necrosis. Tumor cells displayed a high N: C ratio, and high mitotic and apoptotic rates. Tumor nests are often embedded within lymphoid stroma, and may be infiltrated by lymphoid cells.Fifteen cases (15/15) were strongly positive for p16; Ki-67 index were 60%-90%; they were focally positive or negative for p53. Ten cases (10/10) were negative for HPV 6/11 DNA, and one case(1/10) was focally positive for HPV16/18 DNA. Eleven cases (11/11) were strongly positive for HPV16 mRNA, one case was focally positive for HPV18 mRNA. Conclusions: OPSCC-HPV is a pathologically and clinically distinct form of head and neck squamous cell carcinoma. OPSCC-HPV is associated with high-risk HPV (type 16) in all cases. Detection of high-risk HPV16 mRNA by RNAscope is of great significance in the final diagnosis and pathogen identification.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus , Adulto , Idoso , Carcinoma de Células Escamosas/química , Inibidor p16 de Quinase Dependente de Ciclina/análise , Feminino , Neoplasias de Cabeça e Pescoço/química , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Pescoço , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , RNA Mensageiro/análise , RNA Viral/análise , Estudos Retrospectivos , Proteína Supressora de Tumor p53/análise
13.
Braz J Otorhinolaryngol ; 85(1): 11-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29162408

RESUMO

INTRODUCTION: Oral verrucous carcinoma is a special form of well-differentiated squamous cell carcinoma which possesses specific clinical, morphologic and cytokinetic features that differ from other types of oral cancers and hence diagnosis requires immense experience in histopathology. Hence it is certainly important to distinguish such a lesion from other oral tumors as treatment strategies vary widely between them. OBJECTIVE: In search of a critical diagnostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma, Notch4 receptor, one of the key regulatory molecules of the Notch signaling family has been aberrantly activated in the progression of several types of tumors. However its function in oral verrucous carcinoma remains unexplored. Thus the present study aims in determining the differential expression pattern of Notch4 in oral verrucous carcinoma and oral squamous cell carcinoma. METHODS: Ten patients reported positive for oral cancer (5 patients with oral verrucous carcinoma and 5 patients with oral squamous cell carcinoma). Five normal tissue samples were also obtained and evaluated for clinicopathological parameters and immunohistochemistry, western blotting and real time polymerase chain reaction for Notch4 expression. RESULTS: Our results reveal that the expression of Notch4 was considerably high in oral squamous cell carcinoma lesions compared to normal tissue, whereas in oral verrucous carcinoma, irrespective of the clinicopathological features, complete regulação descendente of Notch4 was observed. CONCLUSIONS: These preliminary findings strongly support the fact that Notch4 is downregulated in oral verrucous carcinoma and could be considered as a suitable prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma. This distinguishing marker can help in improving therapeutic options in patients diagnosed with oral verrucous carcinoma.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma Verrucoso/patologia , Neoplasias Bucais/patologia , Receptor Notch4/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Western Blotting , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/diagnóstico , Carcinoma Verrucoso/química , Carcinoma Verrucoso/diagnóstico , Diagnóstico Diferencial , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/química , Neoplasias Bucais/diagnóstico , Prognóstico , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Acta Otorrinolaringol Esp ; 70(1): 16-24, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29573781

RESUMO

BACKGROUND AND OBJECTIVES: We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma. MATERIAL AND METHODS: The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC. RESULTS: Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied. CONCLUSIONS: Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Proteínas de Neoplasias/fisiologia , Neoplasias Nasais/metabolismo , Neoplasias dos Seios Paranasais/metabolismo , Transdução de Sinais , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/mortalidade , Receptores ErbB/fisiologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Nasais/química , Neoplasias Nasais/mortalidade , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/fisiologia , Neoplasias dos Seios Paranasais/química , Neoplasias dos Seios Paranasais/mortalidade , Fosfatidilinositol 3-Quinases/fisiologia , Prognóstico , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteínas Quinases S6 Ribossômicas/fisiologia , Deleção de Sequência , Serina-Treonina Quinases TOR/fisiologia
15.
Int J Radiat Oncol Biol Phys ; 103(1): 152-160, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30121234

RESUMO

PURPOSE: Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus has been implicated as a causative factor for a subset of these patients. The purpose of this study was to evaluate whether p16-positivity (a human papillomavirus surrogate) predicts for better response rates in women who undergo surgery followed by adjuvant radiation therapy (RT). METHODS AND MATERIALS: We retrospectively analyzed data from women with VSCC who were treated with adjuvant RT. p16-Positivity was defined as diffuse strong immunoreactivity within the tumor. Time to event outcomes was performed with Kaplan-Meier and cumulative incidence methodologies. RESULTS: Thirty-nine women were identified. Ten had positive results for p16 (p16+), and 29 had negative results (p16-). The median follow-up was 25.7 months. The median age at diagnosis was 59 years for women with p16+ tumors and 74 years for women with p16- tumors (P = .022). The distribution of stage did not differ by p16 status. The indications for adjuvant RT were close/positive margins in 19 women, positive nodes in 9 women, and both in 11 women. There were 21 recurrences: 15 vulvar, 3 isolated nodal, 2 synchronous vulvar/nodal, and 1 distant metastasis. In-field relapse rates at 3 years were lower in p16+ patients (32.5%) than in p16- patients (59.1%, P = .072). This trend was also observed in progression-free survival (P = .062). A p16+ status and a lower International Federation of Gynecology and Obstetrics stage were associated with fewer in-field relapses and improved progression-free survival in multivariable analyses. The p16 status was not a predictor of overall survival. CONCLUSIONS: p16-Positivity appears to be a prognostic factor for in-field relapse rates in patients with VSCC appropriately treated with adjuvant RT.


Assuntos
Carcinoma de Células Escamosas/terapia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Neoplasias Vulvares/terapia , Vulvectomia , Idoso , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Vulvares/química , Neoplasias Vulvares/mortalidade
16.
Turk Patoloji Derg ; 35(3): 237-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28832076

RESUMO

The term collision tumor is used to describe two neoplasms occurring in the same anatomic location with juxtaposition of different tumor elements. Such a coexistence of tumors anywhere in the body is relatively rare. We report a case of 32-year-old female with collision tumor of rectum. The tumor showed two distinct histological patterns with predominant component consisting of malignant melanoma and a minor component of squamous cell carcinoma. The morphological picture of collision was further confirmed by specific immunohistochemical profile of the two tumors. Collision tumors of rectum are uncommon with most of the reported cases comprising adenocarcinoma and neuroendocrine tumors. To the best of our knowledge this is the first case of collision tumor of malignant melanoma and squamous cell carcinoma in the rectum.


Assuntos
Carcinoma de Células Escamosas/patologia , Melanoma/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Retais/patologia , Biomarcadores Tumorais/análise , Biópsia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Melanoma/química , Melanoma/cirurgia , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Retais/química , Neoplasias Retais/cirurgia
17.
Gynecol Oncol ; 152(1): 208-217, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30415992

RESUMO

The tumor suppressor proteins p16 and p53 have been suggested to have prognostic value in some human papillomavirus (HPV)-associated cancers, however, this has been less well established for vulvar cancer. The aim of this review and meta-analysis was to examine the prognostic value of p16 and p53 expression status on survival after vulvar squamous cell carcinoma (VSCC). We conducted a thorough systematic literature search of multiple databases to identify studies examining survival after histolocally verified VSCC that were tested for p16 and/or p53. A total of 18 eligible studies were included. Using a fixed-effects model we calculated study-specific and pooled hazard ratios (HRs) of 5-year overall survival (OS). In the analyses of OS, we included 475 VSCC cases tested for p16 expression of which 38% were p16 positive. The pooled HRp16 was 0.40 (95% CI: 0.29-0.55). In addition, the majority of results from studies with adjusted analyses on the prognostic value of p16 indicated that p16 expression status could be an independent prognostic marker for OS in women diagnosed with VSCC, and the same pattern was seen for disease specific survival (DSS). We also included 310 VSCC cases tested for p53 expression of which 54% were p53 positive. The pooled HRp53 was 1.81 (95% CI: 1.22-2.68) indicating that p53 positive VSCC have a significantly lower 5-year OS compared to p53 negative. The results in relation to p53 reported from adjusted analyses OS and on DSS and disease free survival were more equivocal. This meta-analysis and review suggests that p53 and especially p16 expression status are of prognostic importance in women diagnosed with VSCC. This may be clinically important in the future design of targeted therapy and when planning the optimal follow-up strategy. Future studies should include the combined use of biomarkers such as p16, p53 and HPV status.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/análise , Proteína Supressora de Tumor p53/análise , Neoplasias Vulvares/mortalidade , Carcinoma de Células Escamosas/química , Intervalo Livre de Doença , Feminino , Humanos , Prognóstico , Neoplasias Vulvares/química
19.
Clinics (Sao Paulo) ; 73: e361, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30379223

RESUMO

OBJECTIVES: Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases. METHODS: In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant. RESULTS: We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype. CONCLUSIONS: We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/química , Idoso , Biópsia , Carcinoma de Células Escamosas/química , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/química , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Eur J Cancer ; 104: 219-223, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30301582

RESUMO

Assessing tumour response using a traditional phase I, II and III trial approach is not without limitations, particularly when targeted therapies are involved. Window of opportunity trials, performed presurgically but differing from neoadjuvant studies, were developed in an attempt to overcome the limitations of the traditional approach. A recent window of opportunity trial, the EORTC 90111-24111-NOCI-HNCG study, evaluated afatinib in treatment-naive patients with squamous cell carcinoma of the head and neck. While this study was the first to demonstrate the activity of afatinib in this setting and to define its potential predictive biomarkers, it also highlighted the challenges associated with the window of opportunity trial design, including the impact of patient selection, tumour site, and other organisational issues. This report details the key learnings from the EORTC 90111-24111-NOCI-HNCG study and provides recommendations to overcome the challenges of this particular trial design.


Assuntos
Afatinib/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto/métodos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Estudos Multicêntricos como Assunto/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Afatinib/administração & dosagem , Afatinib/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/química , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Comunicação Interdisciplinar , Imagem por Ressonância Magnética/métodos , Equipe de Assistência ao Paciente , Seleção de Pacientes , Pré-Medicação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Garantia da Qualidade dos Cuidados de Saúde , Projetos de Pesquisa , Manejo de Espécimes , Fatores de Tempo , Tomografia Computadorizada por Raios X
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