Tumor suppressor Prdx1 is a prognostic factor in esophageal squamous cell carcinoma patients

Peroxiredoxins (Prdxs) are a family of antioxidant enzymes that are also known as scavengers of peroxide in mammalian cells. Some reports have shown that the overexpression of Prdx1, which is one of the peroxiredoxins that is a ubiquitously expressed protein, was related to a poor prognosis in several types of human cancers. In this study, we investigated the expression levels of Prdx1 in esophageal squamous cell carcinoma by immunohistochemistry, and the correlation between the Prdx1 expression and the clinical status was elucidated. Immunohistochemical staining was performed in 114 samples which were collected from surgical esophageal cancer specimens. Cytoplasmic staining of Prdx1 was evaluated based on the following scoring criteria: Grade I, negative or weak staining; Grade II, moderate staining; and Grade III, strong staining. The percentage of patients with a Grade I expression of Prx1 was 20% (23 of 114), 44% had Grade II (50 of 114), and 36% had Grade III (41 of 114). The Prdx1 immunoreactivity showed an inverse significant correlation with T-category (P<0.0001), lymph node metastasis (P=0.048), and stage (P=0.001). In addition, the patients with tumors exhibiting a reduced Prdx1 expression had shorter overall survival (P=0.022) in comparison to the patients with tumors which had a higher Prdx1 expression. Currently, Prdx1 has been shown to act as a tumor suppressor. Our results provide strong evidence that the reduced Prdx1 expression is an important factor in esophageal squamous cancer progression and could serve as a useful prognostic marker.     

Immunohistochemical expression of hormone receptors and the histological characteristics of biochemically hormone receptor negative breast cancers

Background  Most of the discordant cases between biochemical and immunohistochemical (IHC) assays for hormone receptor (HR) status in breast cancers are due to negative findings from the biochemical assay but positive IHC findings. However determining HR status based on IHC only in biochemically HR negative breast cancers has never been studied. The aim of this study is to examine the histological characteristics in immunohistochemically HR positive but biochemically HR negative breast cancers. Methods  IHC staining for HRs in 345 biochemically HR-negative breast cancers was done. The relationship between HR status by IHC and the histological characteristics was assessed. Results  In 345 cancers, 105 (30.4%) were estrogen receptor- (ER) or progesterone receptor- (PR) positive by IHC. The enzyme-immunoassay (EIA) HR titer was higher in immunohistochemically HR-positive tumors (ER: 2.7 fmol/mg protein; PR: 0.8 fmol/mg protein) than in negative tumors (0.6 fmol/mg protein in both HRs). IHC-assessed ER positivity on histological sections was high in some tumor types, such as mucinous carcinoma (77.8%), invasive micropapillary carcinoma (66.7%), and infiltrating ductal carcinoma of no special type with abundant stroma (60.2%). Among infiltrating ductal carcinomas of no special type, low nuclear grade tumors were all ER positive and high nuclear grade tumors showed low ER positivity by IHC, even in biochemically HR negative cancers. Conclusion  The IHC-assessed HR status may reflect tumor cell behavior, such as overall and disease-free survival and endocrine response, better than HR status as assessed by the enzyme-immunoassay method. Immunohistochemically HR-positive but biochemically HR-negative breast cancers include infiltrating ductal carcinomas of no special type with low nuclear grade and some tumor types with high stromal content. We can assess the true HR status by IHC especially these tumors.     

Impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy: 3-year longitudinal study

PURPOSE: We conducted a 3-year longitudinal study assessing the impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy. MATERIALS AND METHODS: A total of 113 patients undergoing radical retropubic prostatectomy were classified into 3 groups according to the degree of nerve sparing, that is unilateral nerve preservation with contralateral sural nerve graft interposition, bilateral nerve sparing and unilateral nerve sparing. Urinary continence and potency were estimated by the UCLA Prostate Cancer Index questionnaire. RESULTS: Patients in the nerve sparing plus sural nerve graft group were younger than those in the bilateral nerve sparing or unilateral nerve sparing groups. At baseline the unilateral nerve sparing plus sural nerve graft group and the bilateral nerve sparing group reported better sexual function than the unilateral nerve sparing group (62.1 and 61.5 vs 49.9, p<0.05). The bilateral nerve sparing group showed more rapid recovery than the unilateral nerve sparing plus sural nerve graft group after radical retropubic prostatectomy (p<0.01). After 24 months there were no significant differences observed between the bilateral nerve sparing and the unilateral nerve sparing plus sural nerve graft group (28.7 vs 32.9). The bilateral nerve sparing group reported a better sexual function score than the unilateral nerve sparing group throughout the postoperative period (p<0.05). The bilateral nerve sparing group maintained significantly better urinary function at 1 month after radical retropubic prostatectomy than the unilateral nerve sparing plus sural nerve graft group (p <0.05). After 3 months these groups were almost continent. The unilateral nerve sparing group reported lower urinary function scores during the first year compared to the other groups. CONCLUSIONS: The nerve graft procedure may contribute to the recovery of urinary function as well as sexual function after radical retropubic prostatectomy. This finding needs to be validated in a randomized trial.     

The effect of neoadjuvant chemotherapy on lymph node micrometastases in squamous cell carcinomas of the thoracic esophagus

BACKGROUND: Neoadjuvant chemotherapy (NACT) has been postulated but not yet proven to eradicate micrometastases and improve the prognosis of patients with advanced esophageal squamous cell carcinomas (ESCC). Cytokeratin immunohistochemistry of the lymph nodes of ESCC revealed immunohistochemical micrometastases (IHM) and cytokeratin deposits (CD), which are hyalinized denucleated particles considered to be cadavers of carcinoma cells. Successful chemotherapy should convert cancer cells from IHM to CD and improve the status of ESCC patients from systemic disease to regional disease. METHODS: Cytokeratin immunostaining of surgically removed lymph nodes was performed for 107 patients with node-positive ESCC, including 32 patients without preoperative treatment (Surgery group) and 75 patients undergoing NACT using CDDP, doxorubicin hydrochroride, and 5-fluorouracil (NACT group). Cytokeratin-positive staining was done for serial hematoxylin-eosin-stained sections and classified as pathologic metastasis, IHM, or CD. RESULTS: CD was observed less frequently in the Surgery group than in the NACT group (6% vs 43%, P < .0001), whereas IHM was more frequent in the former (47% vs 24%, P = .019). IHM was a poor prognostic factor in both groups, whereas CD was a favorable one in the NACT group. The effect of chemotherapy on IHM was classified as eradicated, IHM(-)/CD(+); persistent, IHM(+)/CD(+); no effect, IHM(+)/CD(-); or not informative, IHM(-)/CD(-). This classification correlated well with the clinical response of the primary neoplasm, number of pathologic metastases, and postoperative survival (3-year survival rates: 78%, 18%, 0%, and 38%). IHM/CD was found to be an independent prognostic factor together with the number of pathologic metastases in the multivariate analysis. CONCLUSIONS: Disappearance of IHM and the emergence of CD suggest the eradication of micrometastases by NACT. The clinical benefit of NACT was apparent for IHM(-)/CD(+) patients with node-positive ESCC.     

Geriatric nutritional risk index as an easy-to-use assessment tool for nutritional status in hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Aim

The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy-to-use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC).

Methods

A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child–Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI.

Results

Atez/Bev was used in 338 of the present cohort as first-line systemic chemotherapy (64.4%). Median progression-free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c-index) values of GNRI for predicting prognosis (progression-free survival/overall survival) were superior to those of Child–Pugh class and albumin-bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649–0.781; specificity/sensitivity = 0.644/0.688).

Conclusion

These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev.     

N-terminus of Etanercept is Proteolytically Processed by Dipeptidyl Peptidase-4

Pharmaceutical Research - Biologics are structurally heterogeneous and can undergo biotransformation in the body. Etanercept (ETN) is a fusion protein composed of a soluble tumor necrosis factor...