Immunoexpression of HSPA9 and CUL2 in prostatic tissue and adenocarcinoma.

CUL2 plays a crucial role in proteolysis by preserving the balance between normal growth and uncontrolled proliferation. HSPA9 safeguards the integrity of protein interactions and supports cellular homeostasis. In carcinomas, HSPA9 and CUL2 appear to protect neoplastic cells from internal and external damage. In prostate tumors they are apparently associated with increased risk of unfavorable outcomes, but information remains scarce. In this study we evaluated CUL2 and HSPA9 expression in neoplastic and non-neoplastic prostate tissue and Gleason pattern 3 and 4 adenocarcinoma to identify associations with ISUP prognostic groups and postoperative disease progression. The records of 636 radical prostatectomy patients were reviewed retrospectively and microarrays were mounted with paraffin-embedded adenocarcinoma and non-neoplastic tissue. We evaluated the ability of HSPA9 and CUL2 to predict postoperative PSA outcomes, response to adjuvant/salvage therapy and systemic disease. HSPA9 and CUL2 were diffusely expressed. HSPA9 expression was associated with increased risk of high-grade adenocarcinoma, while HSPA9 and CUL2 were associated with biochemical failure after salvage therapy. In conclusion, HSPA9 and CUL2 were highly expressed in prostate tissue, especially in neoplastic cells. HSPA9 and CUL2-positive Gleason pattern 3 adenocarcinoma was more likely to be associated with Gleason pattern 4 or 5, while HSPA9 and CUL2-positive Gleason pattern 4 adenocarcinoma was less likely to belong to ISUP groups 1 and 2. Staining for HSPA9 and CUL2 can help identify patients at increased risk of recurrence after salvage therapy.

Prognostic value of FUS immunoexpression for Gleason patterns and prostatic adenocarcinoma progression.

BACKGROUND: Risk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. PATIENTS AND METHODS: Non-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. RESULTS: Our cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203-2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878-1.499]; p = 0.313). CONCLUSION: Non-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.

PanCD44 Immunohistochemical Evaluation in Prostatectomies from Patients with Adenocarcinoma.

INTRODUCTION: CD44 has been proposed as a prognostic marker and a stem cell marker but studies in patients with prostate cancer have yielded inconsistent results. PATIENTS AND METHODS: Patients submitted to radical prostatectomy between 2008 and 2013 at a university hospital were followed with biannual serum PSA tests to determine the biochemical recurrence (BR). Archived paraffin blocks with neoplastic and nonneoplastic tissue were evaluated immunohistochemically for a panCD44 and MYC. RESULTS: Sixty-nine patients completed follow-up and were included. CD44 positivity was observed in inflammatory cells (42%), nonneoplastic epithelium (39.7%), and neoplastic tissue (12.3%). In nonneoplastic tissues staining was observed in basal and luminal cells with the morphology of terminally differentiated cells. In neoplastic tissues, CD44 negativity was correlated with higher Gleason scores (Rho = -0.204; p = 0.042) and higher preoperative serum PSA levels when evaluated continuously (p = 0.029). CD44 expression was not associated with tumor stage (p = 0.668), surgical margin status (p = 0.471), or BR (p = 0.346), nor was there any association between CD44 and MYC expression in neoplastic tissue (p = 1.0). CONCLUSION: In the bulk of cells, the minority of cancer stem cells would not be detected by immunohistochemistry using panCD44. As a prognostic marker, its expression was weakly correlated with Gleason score and preoperative PSA level, but not with surgical margin status, tumor stage, or BR.

The association among HER2, MET and FOXP3 expression and tumor regression grading in gastric adenocarcinoma.

Although the introduction of the perioperative chemotherapy on the management of gastric cancer has improved patients survival, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Thus, this study evaluated the tumor regression grading (TRG) in a series of post-treatment gastric tumors and its associations with HER2, MET, and FOXP3 expression. Material of 54 gastric cancer samples was available for TRG evaluation and immunohistochemistry. We found that total and subtotal pathologic response were significantly associated to the intestinal subtype (p = 0.04) and that well-differentiated tumors were significantly correlated with total or partial response (p = 0.019). Although not associated with the TRG, FOXP3 expression in gastric tumors was associated to poorly differentiated tumors (p = 0.03), to the diffuse and mixed subtypes together (p = 0.04) and to the presence of vascular infiltration (p = 0.04), while HER2 overexpression was associated to better differentiated cases (p = 0.04) and to the absence of vascular infiltration (p = 0.02). MET expression, however, showed no association with the analyzed clinicopathological factors. This study highlights the role of tissue differentiation on pathological response to neoadjuvant chemotherapy in gastric cancer and shows no impact between FOXP3, HER2 and MET expression in terms of TRG.

Histopathological regression of gastric adenocarcinoma after neoadjuvant therapy: a critical review.

As the perioperative chemotherapy has been widely implemented on the management of gastric cancer patients, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Tumor histological response to preoperative therapy has been graded by various systems in order to categorize the amount of regressive changes induced by chemotherapy in relation to residual tumor. In this context, tumor regression grading (TRG) systems might provide important prognostic information as the variety of tumor response may imply on different clinical outcomes with impact in survival rates. Moreover, gastric cancer behavior varies enormously upon individual factors such as histological classification and tumor anatomic site of involvement that have been shown to affect the TRG interpretation. On the other hand, some studies have assessed the role of molecular markers as a predictor of tumor response to neoadjuvant chemotherapy in terms of TRG. Thus, the aim of this review is to evaluate how TRG has been interpreted in gastric cancer, discuss their clinical and prognostic relevance and also address the molecular markers involved in this process.

[Tensional and morphologic analysis of the colonic anastomosis on 10% acetic acid induced colitis, in Wistar rats, treated with 10% aroeira-do-sertão (Myracrodruon urundeuva fr. all.) aqueous extract]. / Análise tensional e morfológica da anastomose colônica na colite induzida por ácido acético a 10%, em ratos Wistar, tratados com extrato aquoso de aroeira-do-sertão a 10% (Myracrodruon urundeuva fr. all.).

PURPOSE: Verify, from a morphologic and tensional view point, the effect of the 10% aqueous extract of aroeira-do-sertão on the colonic anastomosis, during the occurrence of 10% acetic acid induced colitis, in Wistar rats. METHODS: There were used 48 Wistar rats, distributed in two groups. All animals were subjected to induction of colitis by aqueous solution of 10% acetic acid. Twenty-four hours later, the animals were subjected to laparotomy, transverse total colotomy and end-to-end anastomosis with 5-0 polypropylene. Group A (vehicle), animals treated with carboxymethylcellulose based vehicle. Group B (aroeira), animals treated with 10% aroeira aqueous extract. Both treatments were by means of enema. Groups A and B were distributed in subgroups A3, A7, A14 and A21; B3, B7, B 14 and B21, according to the foreseen euthanasia date (days 3, 7, 14 and 21). On these dates, the animals were relaparotomized, the colonic segment containing the anastomosis was ressected subjected to the pressure test and then to the, histological analysis. For the momphologic study, the slides were dyed with hematoxilin-eosine and the healing status was evaluated based on a score chart that ranked from 0 to 16. The higher the score, the better the healing. RESULTS: On the evaluation of the morphologic study, which quantifies the evolution and degree of healing, as a final result of the healing process, the group aroeira was superior to the group vehicle (p<0.05) on the twenty-first day, showing higher velocity on tissue repair that occurs by regeneration and not by fibrosis. With respect to the tension test, there was a statistically significant difference on day 3, with predominance of the group aroeira over the group vehicle (p<0.05). CONCLUSION: The 10% aroeira-do-sertão aqueous extract, has healing activity on the colonic anstomosis during the occurrence of 10% acetic acid induced colitis. It improves the resistance to tension on the colonic anastomosis zone on the 3rd day.