Aryl hydrocarbon receptor interacting protein (AIP) significantly influences prognosis of pancreatic carcinoma.

INTRODUCTION: Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. Aryl hydrocarbon receptor interacting protein (AIP) in one of AHR ligands. The aim of this study is to analyze the prognostic influence of AIP in pancreatic carcinoma. MATERIAL AND METHODS: Retrospective case series with immunohistochemical analysis of AIP. We have estimated a multivariate Cox's model for the outcome (progression free and overall survival). RESULTS: 204 patients were included in the study. As expected prognosis was poor and 67.8% died of disease. As for AIP 9.8% of the cases showed nuclear staining of the epithelial tumor cells and 59.4% a cytoplasmic one. Stroma was stained in 53.1% of the cases. Univariate survival analysis revealed a significantly worse prognosis of patients with cytoplasmic AIP expression (stroma and epithelium), but nuclear expression was associated to a better prognosis. In the multivariate analysis stromal AIP expression was an independent prognosticator of progression free survival, together with pT stage, histological grade and history of diabetes. DISCUSSION: AIP Is a conserved cochaperone protein binding to many proteins. AIP has been proposed as a potential tumor suppressor gene. To date, no study has analyzed the immunohistochemical expression of AIP in pancreatic carcinoma. Our results indicate that both epithelial and stromal cytoplasmic expression of AIP is associated to bad prognosis, while nuclear translocation seems to improve prognosis. CONCLUSION: Although we must deepen into the complex signaling pathways underlying this potential association, our results open a way to inhibiting AHR as a potential target against pancreatic carcinoma.

Colorectal cribriform comedo-type adenocarcinoma: a distinct subtype with poor prognosis?

Colorectal cancer is one of the most commonly diagnosed cancers in the world. It is a heterogeneous disease with several histologic subtypes, and some of them are associated with adverse prognostic factors. Cribriform comedo-type adenocarcinoma (CCA) has been included as a colorectal adenocarcinoma subtype in the last World Health Organization (WHO) classification of gastrointestinal system tumors. Some authors have linked this subtype to an adverse prognosis, but to the best of our knowledge there is only one previous report assessing its histologic and prognostic features. We herein review a series of CCA of the colon, emphasizing its clinical and morphological features.

Anal cytology in women: Experience from a single tertiary center.

INTRODUCTION: Anal cytology (AC) can be used as a screening tool for detection of anal HPV associated lesions, mainly in men who have sex with men and in immunosuppressed patients. Our aim is to review our experience with AC in women. MATERIAL & METHODS: We have retrospectively reviewed all AC diagnosed between 2010-2017 in a single tertiary hospital (n = 644) and selected those performed in women (n = 158). RESULTS: 24.53% of AC were performed in women. 14.7% of all women were HIV positive and 56.7% referred anal intercourse. Squamous lesions were found in 27.2% of women, most of them ASCUS and LSIL (14% and 11.5%). HPV DNA was detected in 38.6% of patients, and 63.9% of them showed positivity for multiple high-risk types. Anal biopsy showed high grade lesions in 20% of biopsied patients. We observed a significant relationship between HPV status and receptive anal sex, and the association between HPV status and anal histological diagnosis tended to significance. Sensitivity, specificity, negative predictive value and positive predictive value for anal cytology were 57%; 83%; 28% and 94%, respectively. 70.9% of women had synchronous cervical cytology, and squamous cervical lesions were detected in 46.4% of the cases, most of them LSIL or ASCUS (21.4% and 15.2%). We did not confirm a significant association between cytological diagnosis of cervical and anal samples. CONCLUSIONS: AC is less widely used in women than in homosexual men. However, women show important rates of anal lesions, regardless of their HIV status. More studies should be performed to assess the potential impact of screening protocols in this population.

Globular amyloidosis of the colon.

Gastrointestinal involvement is frequent in systemic amyloidosis. However, amyloidosis can rarely be confined to the gastrointestinal tract or appear as a tumour mass. There have been few reports describing amyloid globular deposits in a variety of locations, as opposed to the usual linear ones. We herein report a rare case of globular amyloidosis involving the large bowel, which to the best of our knowledge is the second reported in the world literature. A 74-year-old man consulted on anaemia. Endoscopy showed ulcerative lesions in the left colon, which were biopsied and diagnosed as ischemic colitis. Under light microscopy, we found globular discrete deposits in the lamina propria which were Congo red-positive and resistant to permanganate digestion. Histopathological diagnosis was globular amyloidosis with AL deposits. The patient underwent further studies, including a haematologic evaluation that discarded systemic involvement. Globular amyloidosis seems to be a rare morphologic type of amyloidosis, but not a distinct entity. Its etiology, pathogenesis and relationship with patient prognosis and disease severity remain largely unknown. When amyloid deposits are confined to the gastrointestinal tract, systemic therapy can be avoided and patients should only be followed periodically. Immunohistochemical classification and clinical correlation are essential to rule out systemic amyloidosis.

Histopathological factors predicting response to neoadjuvant therapy in gastric carcinoma.

BACKGROUND: Neoadjuvant therapy (NAT) is a useful therapeutic option. However, some patients respond poorly to it and can even show tumor progression. It is important to define factors that can predict response to NAT. MATERIALS AND METHODS: This is a retrospective cohort study to define histopathological factors predicting response to NAT in gastric tubular carcinoma. This study has enrolled 80 patients receiving chemotherapy for locally advanced gastric carcinoma. RESULTS: 44.5% of the patients were men; mean age was 64.49 years. Only 5.7% of the patients showed a complete response to therapy, 10% had grade 1, 21.4% grade 2, and 62.9% grade 3 regression. On follow-up, 43.8% of the patients showed recurrence of disease (57.1% distant metastasis) and 33.8% eventually died of it. We found a statistically significant association between response and prognosis. We found a statistically significant association between regression and perineural, vascular, and lymph vessel invasion. Logistic regression model showed that only lymph vessel invasion had independent influence. Lymph vessel invasion not only indicated lack of response to therapy, but also higher incidence of lymph node involvement in the gastrectomy specimen. DISCUSSION: Our study indicates that the presence of vascular or perineural invasion in the endoscopic biopsies and high histopathological grade predict poor response to therapy. This seems peculiar, for undifferentiated tumors are supposed to have better response to therapy. CONCLUSION: Our study indicates that undifferentiated tumors respond worse to therapy. Furthermore, studies are necessary to define lack of response, to help avoid neoadjuvant therapy in unfavorable cases.

CPEB4 immunohistochemical expression is associated to prognosis in stage IV colorectal carcinoma.

The cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a RNA binding protein and translational regulator. It has been associated with tumor growth, vascularization and invasion and with tumor progression in breast, pancreas and lung carcinomas. To the best of our knowledge only one previous report has analyzed the prognostic value of CPEB4 in an experimental model of colorectal carcinoma. We have reviewed the files of patients with stage IV colorectal carcinoma metastatic to the liver. All the patients had received chemotherapy followed by hepatic metastasis resection and subsequent resection of the colon (liver-first approach). We have gathered demographic, analytical and morphological data of the primary tumors. We have performed immunohistochemical analysis of CPEB4 expression in these tumors and analyzed the potential prognostic value of this protein. 50 patients fulfilled inclusion criteria for the present study. All of them received preoperative chemotherapy based on platinum and also postoperative chemotherapy, with or without targeted drugs (18% received anti-epidermal growth factor receptor (EGFR) drugs and 24% anti-vascular endothelial growth factor receptor (VEGFR) drugs. 66% of the primaries were of sigmoid-rectal origin. CPEB4 expression was mainly cytoplasmic and it was scored as intense in 46% of the patients. Survival analysis revealed a significant association between progression free survival (PFS) and overall survival (OS) and CPEB4 immunohistochemical expression, which was independent in the multivariate analysis. CPEB4 behaves as a significant predictor of prognosis in stage IV colorectal carcinoma. The existence of CPEB4 specific inhibitors can open a new way for targeted therapy. Larger prospective studies are needed to confirm our promising results.