Neuropilin-2 is an independent prognostic factor for shorter cancer-specific survival in patients with acinar adenocarcinoma of the prostate.

Neuropilin-2 (NRP2) is a member of the neuropilin receptor family and known to regulate autophagy and mTORC2 signaling in prostate cancer (PCa). Our study investigated the association of immunohistochemical NRP2 expression with clinicopathological data in PCa patients. For this purpose, we generated a tissue microarray with prostate tissue specimens from 400 PCa patients treated by radical prostatectomy. We focused on patients with high-risk factors such as extraprostatic extension (pT ≥ 3), Gleason score ≥8 and/or the presence of regional lymph node metastases (pN1). Protein levels of NRP2, the vascular endothelial growth factor C (VEGFC) and oncogenic v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene as an indicator for TMPRSS2-ERG fusion was assessed in relation to the patients' outcome. NRP2 emerged as an independent prognostic factor for cancer-specific survival (CSS) (hazard ratio 2.360, 95% confidence interval = 1.2-4.8; p = 0.016). Moreover, the association between NRP2 expression and shorter CSS was also especially pronounced in patients at high risk for progression (log-rank test: p = 0.010). We evaluated the association between NRP2 and the TMPRSS2-ERG gene fusion status assessed by immunohistochemical nuclear ERG staining. However, ERG staining alone did not show any prognostic significance. NRP2 immunostaining is significantly associated with shorter CSS in ERG-negative tumors (log-rank test: p = 0.012). No prognostic impact of NRP2 expression on CSS was observed in ERG-positive tumors (log-rank test: p = 0.153). Our study identifies NRP2 as an important prognostic marker for a worse clinical outcome especially in patients with a high-risk PCa and in patients with ERG-negative PCa.

Head & neck acinar cell carcinoma: a population-based study using the seer registry.

BACKGROUND: To explore the clinicopathologic characteristics, treatment and prognostic factors of head and neck acinar cell carcinoma (HNACC) comprehensively. METHODS: A population-based study was conducted using data from the Surveillance, Epidemiology, and End Results database (1975-2016). Overall survival (OS) and HNACC-specific survival of patients with different clinicopathologic variables were compared using the Kaplan-Meier method and Cox multivariate regression. RESULTS: A total of 2624 primary HNACC cases (1052 males, 1572 females) were identified. There was a significant difference in gender distribution. Among the total cohort, 2416 cases originated from salivary glands, including 2325 parotid gland ACC cases. Regardless of confounding factors, the 10-year and 20-year disease-specific survival (DSS) was 93.6 and 90%, respectively. Surgery was favourably associated with better DSS and OS [HR = 0.13, P = 0.0092 and HR = 0.23, P = 0.0203]. Gender was the only demographic independent prognostic factor for both DSS and OS [Male vs female, HR = 3.3, P = 0.0028 for DSS; HR = 2.44, P = 0.0376 for OS]. Higher pathological grade was adversely associated with DSS and OS [Grade II, HR = 4.03, P = 0.0444; Grade III + IV, HR = 35.64, P = 0.0000 for DSS; Grade III + IV, HR = 4.49, P = 0.0000 for OS, Grade I as reference]. In addition, TNM/AJCC stage was commonly associated with prognosis. CONCLUSION: Surgery was the only favourable prognostic indicator for both DSS and OS. Gender, age, pathological differentiation and TNM/AJCC stage were independent prognostic factors for survival.

Clinical Analysis of Acinar Cell Carcinoma of the Pancreas: A Single-Center Experience of 45 Consecutive Cases.

BACKGROUNDS: Acinar cell carcinoma of the pancreas is a rare malignancy, and its features remain unclear. We aimed to analyze the clinical characteristics, treatment and prognosis of acinar cell carcinoma with our institutional case series. METHODS: Patients diagnosed with acinar cell carcinoma in our hospital between 2005 and 2019 were reviewed. Investigations on clinicopathological features, treatment details and long-term survival were performed. RESULTS: A total of 45 pathologically confirmed acinar cell carcinomas were identified. The median age at diagnosis was 58 years with a male-to-female ratio of 3.1:1. There were 24 (53.3%) localized, 5 (11.1%) locally advanced and 16 (35.6%) metastatic cases, with a pancreatic head-to-body/tail ratio of 1:1.4 for all the primary lesions. In the localized group, there were 10 pancreatoduodenectomy, 12 distal pancreatectomy, 1 total pancreatectomy, and 1 distal pancreatectomy combined with proximal gastrectomy. Among the locally advanced and metastatic cases, 13 patients received chemotherapy, 1 received concurrent radiochemotherapy, 1 underwent synchronous resection of primary tumor and liver metastasis, 1 underwent palliative operation, 1 underwent exploratory laparotomy, and 4 required no treatment. The median overall survival of this series was 18.9 months with a 5-year survival rate of 19.6%. Moreover, the resected acinar cell carcinoma patients were associated with prolonged survival compared with the unresected cases (36.6 vs. 8.5 months, P < 0.001). CONCLUSIONS: Surgical resection could improve the long-term survival of acinar cell carcinoma patients, which might also improve the prognosis of selected metastatic cases. Large-scale studies are needed to further clarify the biological behavior and clinical features, and to seek the optimal treatments.

Efficacy of surgery combined with postoperative 125 I interstitial brachytherapy for treatment of acinic cell carcinoma of the parotid gland in children and adolescents.

BACKGROUND: Acinic cell carcinoma (AciCC) is rare in children; therefore, reaching a consensus on its management is challenging and radiotherapy is limited by concerns about long-term toxicity. The purpose of this study is to analyze the effectiveness and safety of surgery plus postoperative 125 I interstitial brachytherapy (IBT) for children and adolescents with AciCC of the parotid gland (PG) treated at a single institution. PROCEDURE: Sixteen patients ≤ 18 years old with AciCC of the PG treated with surgery plus 125 I IBT from 2007 to 2018 were included. Surgery was the primary treatment; ten patients underwent total gross excision and six subtotal gross excision. The matched peripheral dose was 60-120 Gy. Overall survival, disease-free survival (DFS), local control rate, distant metastasis, and radiation-associated toxicities were analyzed, and factors influencing outcomes were evaluated. RESULTS: During follow-up (1.8-12.6 years; mean, 6.3 years), lymph node metastasis was observed in one case, 2.6 years after 125 I IBT treatment. The five-year overall and DFS rates were 100% and 91.7%, respectively. On univariate analysis, tumor size ≥ 3 cm (100% vs 50%; P = 0.025) and extraglandular extension (100% vs 50%; P = 0.025) were significant prognostic indicators for DFS. No severe radiation-associated complications occurred. CONCLUSIONS: Children and adolescents with AciCC of the PG with high-risk features can be managed using surgery plus postoperative 125 I IBT with excellent local control. Radiation-related complications were minor. Patients with facial nerve involvement can have their facial nerves preserved. Residual tumors can be safely managed using adjuvant 125 I IBT.

Intermediate-grade carcinoma of the parotid and the impact of adjuvant radiation.

PURPOSE: To determine the influence of adjuvant radiotherapy on survival in surgically-managed early stage intermediate-grade mucoepidermoid and acinic cell carcinoma of the parotid. MATERIALS AND METHODS: The National Cancer Database was reviewed between 2004 and 2015 to identify patients with intermediate-grade, early T-stage, node-negative parotid carcinoma who underwent parotidectomy ± radiotherapy. RESULTS: There were 744 patients identified of which 81% had mucoepidermoid carcinoma and 19% had acinic cell carcinoma. Positive surgical margins were identified in 21% and adjuvant radiotherapy was administered in 38% of cases. Of the 159 patients with positive margins, 113 (71%) received adjuvant radiotherapy. Of the 585 patients with negative margins, 173 (30%) underwent adjuvant radiotherapy. In multivariable analysis, age (over 52 years: HR 5.19, 95%CI 2.33-11.57), insurance status (private insurance: HR 0.24 95%CI 0.13-0.43), and extent of parotidectomy (total parotidectomy: HR 2.02 95%CI 1.23-3.31) were significantly associated with overall survival, while adjuvant radiotherapy was not a significant predictive factor (HR 0.81, 95%CI 0.49-1.36). In patients with positive margin resections, however, adjuvant radiation was an independent predictor of improved survival when adjusted for age, insurance status, and extent of parotidectomy (HR 0.34, 95%CI 0.13-0.88). Conversely, in patients with negative margin resections, adjuvant radiation did not influence survival outcomes when adjusted for these covariates (HR 1.02, 95%CI 0.53-1.93). CONCLUSIONS AND RELEVANCE: In patients with early stage intermediate-grade parotid carcinoma, adjuvant radiotherapy significantly and independently improves survival in those with post-operative positive margins. Adjuvant therapy, however, does not appear to improve survival outcomes in those with negative margin resections.

Tightly controlled MRTF-A activity regulates epithelial differentiation during formation of mammary acini.

BACKGROUND: Myocardin-related transcription factors (MRTF) A and B link actin dynamics and mechanotransduction to gene expression. In mice, MRTF-A is involved in mammary gland differentiation, but its role in human mammary epithelial cells remains unclear. METHODS: Three-dimensional cultures of human mammary epithelial MCF10A cells were used to model acinar morphogenesis. Stable MRTF-A knockdown, MRTF-A/B rescue and MRTF-A/B overexpression was established to characterize the functional role during morphogenesis using confocal microscopy and expression analysis. Breast cancer patient databases were analyzed for MRTF-A expression. RESULTS: We showed that a precise temporal control of MRTFs is required for normal morphogenesis of MCF10A mammary acini. MRTF transcriptional activity, but not their protein amounts, is transiently induced during 3D acini formation. MRTF-A knockdown dramatically reduces acini size and prevents lumen formation. These effects are rescued by re-expression of MRTF-A, and partially by MRTF-B. Conversely, overexpression of MRTF-A and MRTF-B increases acini size, resulting in irregular spheroids without lumen and defective apico-basal polarity. These phenotypes correlate with deregulated expression of cell cycle inhibitors p21/Waf1, p27/Kip1 and altered phosphorylation of retinoblastoma protein. In MRTF overexpressing spheroids, proliferation and apoptosis are simultaneously increased at late stages, whilst neither occurs in control acini. MRTFs interfere with anoikis of the inner cells and cause an integrin switch from α6 to α5, repression of E-cadherin and induction of mesenchymal markers vimentin, Snai2 and Zeb1. Moreover, MRTF-overexpressing spheroids are insensitive to alteration in matrix stiffness. In two breast cancer cohorts, high expression of MRTF-A and known target genes was associated with decreased patient survival. CONCLUSION: MRTF-A is required for proliferation and formation of mammary acini from luminal epithelial cells. Conversely, elevated MRTF activity results in pre-malignant spheroid formation due to defective proliferation, polarity loss and epithelial-mesenchymal transition.

Prognostic Factors Associated With Decreased Survival in Patients With Acinic Cell Carcinoma of the Parotid Gland.

PURPOSE: Acinic cell carcinoma (ACC) of the parotid gland is relatively rare. This study aimed to estimate 5-year survival and to identify prognostic factors associated with survival of ACC of the parotid gland. MATERIALS AND METHODS: Thirty-seven patients with ACC of the parotid gland were included in this retrospective cohort study. They were treated in Beijing Stomatological Hospital from January 2000 to December 2011. Predictor variables, including age, gender, tumor stage, nodal stage, perineural invasion, and margin status, were analyzed. The Cox regression model was used to determine prognostic factors for overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 37 patients, 20 were men (54.1%). Mean age was 42 years (range, 13 to 73 yr). Six patients (16.2%) had T3 or T4 tumors and 5 (13.5%) had positive neck nodes. The 5-year OS and DFS were 86.5 and 78.3%, respectively. Positive margin status was associated with worse OS. Patients older than 60 years with a fixed mass, high-grade tumor and nodal stage, perineural invasion, and angiolymphatic invasion had adverse OS and DFS (P < .05). CONCLUSIONS: The present study identified several important prognostic factors associated with OS and DFS in patients with ACC. These prognostic variables include symptoms at presentation, clinical tumor stage and pathologic nodal status, and histopathology-related factors. All these factors were important in patient therapy and could prolong survival rate.

Prognosis of primary breast salivary gland-type carcinoma: a propensity score-matching analysis with invasive carcinoma of no special type based on the SEER database for years 2010-2020.

BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST). METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST. RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p < 0.05). Nonetheless, tumor grade 3 and higher AJCC stage groups remained as significant independent prognostic factors in multivariate analysis (p < 0.05). The apparent better breast cancer-specific survival of salivary gland-type carcinoma as compared to that of invasive carcinoma, NST, was diminished following adjustment for differences in baseline clinicopathological features and treatment-related variables. CONCLUSIONS: This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.

EGFR and TTF-1 gene amplification in surgically resected lung adenocarcinomas: clinicopathologic significance and effect on response to EGFR-tyrosine kinase inhibitors in recurred cases.

BACKGROUND: Gene amplifications are implicated in cancer development and progression. In this study we investigated the clinicopathologic characteristics associated with EGFR or TTF-1 amplification in lung adenocarcinomas and its prognostic significance. METHODS: We analyzed 118 cases of surgically resected primary lung adenocarcinomas. Amplification of the EGFR or TTF-1 gene was evaluated by fluorescence in situ hybridization and correlated with patients' clinicopathologic features, including disease-free survival (DFS) and overall survival (OS), in all patients and a subset that were TTF-1 positive or had EGFR mutation. Progression-free survival (PFS) also was analyzed among patients with EGFR mutation who had recurred cancer that was treated with EGFR tyrosine kinase inhibitors. RESULTS: EGFR or TTF-1 gene amplification was an independent poor prognostic factor for DFS in all patients (p=0.001), in patients with TTF-1 positivity (p=0.010), and in patients with EGFR mutation (p<0.001) and for OS in patients with TTF-1 positivity (p=0.021) and patients with EGFR mutation (p<0.001). Patients with TTF-1 amplification had a shorter PFS following EGFR TKI treatment (p=0.040). CONCLUSIONS: EGFR or TTF-1 gene amplification was a predictive factor for poor prognosis in terms of DFS and OS, especially in patients with TTF-1 positivity or EGFR mutation. Our results also suggested that TTF-1 amplification might be a predictive marker of poor response to EGFR-TKI therapy in patients with recurrent tumor after surgical resection.

Preservation of the pyloric ring has little value in surgery for pancreatic head cancer: a comparative study comparing three surgical procedures.

BACKGROUND: Pylorus-preserving pancreatoduodenectomy (PPPD) has replaced conventional pancreatoduodenectomy with a distal gastrectomy (cPD) as the most commonly performed procedure. However, there has been no evidence from prospective studies to indicate the overwhelming superiority of PPPD over cPD. A recent report revealed that resection of the pyloric ring reduced the incidence of delayed gastric emptying (DGE) in a randomized controlled trial. METHODS: In 158 patients with pancreatic head cancer, the perioperative outcomes and long-term nutritional consequences were retrospectively compared among three types of pancreatoduodenectomy: cPD; PPPD; and subtotal stomach-preserving pancreatoduodenectomy (SSPPD), in which the pyloric ring and duodenum were removed and more than 90% of the stomach was preserved. RESULTS: The incidence of DGE was significantly higher in the PPPD group than in the cPD and SSPPD groups (27.3 vs. 5.8 and 5.4%, respectively; P = 0.0012). The serum albumin concentration and total lymphocyte count at 1 year postoperatively were significantly higher in the SSPPD group than in the PPPD group (P = 0.0303 and P = 0.0203, respectively). The patients in the SSPPD group showed longer survival times than the patients in the cPD and PPPD groups (median survival times, 21.3, 17.1, and 17.7 months, respectively), although the differences did not reach statistical significance. CONCLUSIONS: Our results suggest that preservation of the pyloric ring without vagal innervation has little significance, and that SSPPD with better perioperative and long-term outcomes is more suitable as a standard procedure for patients with pancreatic head cancer.

The many faces of acinic cell carcinomas of the salivary glands: a study of 40 cases relating histological and immunohistological subtypes to clinical parameters and prognosis.

AIMS: To study the morphological heterogeneity of acinic cell carcinoma (ACC) in correlation with clinicopathological parameters. METHODS AND RESULTS: Forty well-characterized ACCs were classified as solid (n = 20), microcystic (n = 15), papillary-cystic (n = 4) or follicular (n = 1), based on the dominant architectural growth pattern. Fourteen tumours exhibited eosinophilic/clear cell morphology and 18 tumours were rich in zymogen granules (so-called blue dot tumours). High-grade morphology occurred in five tumours. Based on cytokeratin (CK) 7 staining and in analogy to CK7 expression in normal salivary gland epithelia, three distinct histogenetic subtypes were recognized: acinar (CK7-negative; n = 13), ductular (diffuse CK7-positive; n = 11) and mixed ductulo-acinar (10-66% CK7-positive cells; n = 16). Most papillary-cystic tumours displayed ductular differentiation (P = 0.015), whereas blue dot tumours never did (P < 0.001). Analysis of relapse-free survival (RFS) revealed that Stage I tumours had the best prognosis without any relapse in 18 years follow-up (P = 0.06). High-grade tumours were associated with shorter RFS (P = 0.028). Concerning the histogenetic types, monophasic (pure acinar or ductular) tumours were associated with a significantly better RFS than mixed ductulo-acinar tumours (P = 0.008). CONCLUSION: The results underscore the great histological diversity of ACC, and the value of histogenetic subtyping as an additional prognostic factor regarding RFS.

Pancreatic neoplasms in childhood and adolescence.

Pancreatic neoplasms are rare in children and adolescents; thus, our understanding of these tumors is still quite limited. We retrospectively reviewed clinical features and outcomes of all patients below 18 years of age with pancreatic neoplasms who were treated at Asan Medical Center between December 1994 and March 2010. Thirty-two patients were identified. Abdominal pain was the most common symptom. The median duration of diagnostic delay was 21 days. Nineteen patients were diagnosed with solid pseudopapillary tumors, 3 with lymphomas, 2 with pancreatoblastomas, 2 with poorly differentiated carcinomas, 2 with acinar cell cancers, 2 with endocrine tumors, 1 with peripheral (primitive) neuroectodermal tumor, and 1 with hemangioendothelioma. Gross complete resection of the primary tumor was achieved in 24 patients (75%), and 8 patients (25%) received chemotherapy. At a median follow-up of 34 months, the 5-year overall survival rate was 92.0 ± 5.5%. On multivariate analysis, histologic type was the only factor significantly predictive of survival (P=0.009). Patients with poorly differentiated carcinoma showed the worst survival probability. In cases of solid pseudopapillary tumors, surgical resection was generally curative and the prognosis was excellent. Patients with other malignant tumors, however, may require therapeutic strategies other than surgery.

Aggressive approach to acinar cell carcinoma of the pancreas: a single-institution experience and a literature review.

PURPOSE: Acinar cell carcinomas (ACCs) are a rare pancreatic tumor group with no standardized treatment. The aim of the study is to analyze the clinical and pathologic characteristics of our series and to review the current literature. METHODS: Retrospective review of prospectively collected data from 1990 to 2007 included patients who underwent pancreatic resection for histologically proven ACCs. All specimens of ACC were rereviewed by an expert pathologist. Follow-up was updated to October 2009. A literature search was performed by Pubmed and COCHRANE library. RESULTS: Among 1,210 patients who underwent pancreatic resection, we identified nine ACCs. R0 resection was possible for all but one R1. We had no major complications and no mortality. All nine cases were diagnosed as pure ACCs. Five patients received adjuvant chemotherapy. Median overall survival was 31 months, while median disease-free survival was 18 months. All patients developed liver metastases, requiring modification of chemotherapeutic schema, radiofrequency ablation techniques, or reiterate surgery. Currently, only one patient is alive without evidence of disease 85 months after pancreatic resection. One patient is alive 52 months after operation, with evidence of recurrent disease. CONCLUSIONS: ACC represents a rare solid tumor of the pancreas. Prognosis is dismal, although, compared to the more common ductal adenocarcinoma, survival appears to be longer. Patients with metastatic disease might benefit from aggressive multimodality treatments.

Comparison between serous and non-serous ovarian cancer as a prognostic factor in advanced epithelial ovarian carcinoma after primary debulking surgery.

BACKGROUND: Residual tumor size after primary surgery is the most important prognostic factor in advanced ovarian cancer. We conducted a retrospective study in Japanese women to evaluate the association of various residual disease diameters and histological subtypes with overall survival (OS) in patients with residual disease ≥1 cm. METHODS: Demographic and clinicopathological data were obtained from the Tokai Ovarian Tumor Study Group; 294 patients with International Federation of Gynecology and Obstetrics stage III and IV epithelial ovarian carcinoma who had undergone primary debulking surgery between 1986 and 2007 and had ≥1 cm residual tumor were identified. A Cox proportional hazards model was used to assess the association of prognostic factors with OS. RESULTS: Non-serous advanced ovarian cancer was associated with a significant increase in the risk of death. For serous ovarian cancer, residual tumor size was not an independent prognostic factor [multivariate hazard ratio (HR) = 1.63, 95% confidence interval (CI) = 0.96-2.79 (2-5 cm); HR = 1.25, 95% CI = 0.72-2.17 (>5 cm); trend P = 0.480], whereas taxane-based chemotherapy was associated with a better prognosis (HR = 0.66, 95% CI = 0.44-0.99, P = 0.046). For non-serous ovarian cancer, in contrast, residual tumor size was associated with an increased risk of death [multivariate HR = 0.87, 95% CI = 0.36-2.14 (2-5 cm); HR = 2.21, 95% CI = 0.96-5.08 (>5 cm); trend P = 0.067], whereas taxane-based chemotherapy was not a prognostic factor [HR = 0.70, 95% CI = 0.29-1.65, P = 0.409 (taxane-based)]. CONCLUSIONS: Although primary maximal cytoreduction is essential to improving OS in advanced ovarian cancer, our findings suggest the management of patients with suboptimal residual tumor should take into account differences between histological subtypes.

Prognostic factors and survival outcome of primary pulmonary acinar cell carcinoma.

PURPOSE: The objective of our study was to investigate the epidemiologic characteristics and prognostic factors in patients with pulmonary acinar cell carcinoma (PACC). METHODS: PACC patients diagnosed between 1975 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The trend in PACC incidence was assessed using joinpoint regression software. Overall survival (OS) and disease-specific survival (DSS) were evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. RESULTS: A total of 2918 patients were identified with PACC. The mean age was 65.2 ± 8.95 years with a female to male of 1.6:1. The incidence of PACC steadily increased by an annual percentage change (APC) of 3.2% (95% CI 2.1-4.4, p < 0.05). Multivariate Cox regression analysis revealed that age, gender, race, stage, grade, tumor size, number of positive lymph nodes, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for PACC were constructed to predict 1- and 5-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance. CONCLUSION: PACC was rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for PACC were robust and accurate in predicting 1- and 5-year OS and DSS.

Multicenter Retrospective Analysis of Chemotherapy for Advanced Pancreatic Acinar Cell Carcinoma: Potential Efficacy of Platinum- and Irinotecan-Containing Regimens.

OBJECTIVES: The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC). METHODS: Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument. RESULTS: The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23-1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15-1.19; P = 0.09) at least once in the treatment course as compared with those who had not. CONCLUSIONS: Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC.

Matrix metalloproteinase (MMP)-7 in salivary gland cancer.

INTRODUCTION: High levels of certain matrix metalloproteinases (MMPs) have been detected in various human cancers. The purpose of this study was to analyze the expression of MMP-7 in salivary gland cancer (SGC) by immunohistochemistry and to associate the results with the clinical data and the 10-year survival of the SGC patients. MATERIAL AND METHODS: Immunohistochemistry for MMP-7 was performed in a series of 107 paraffin-embedded sections of SGC. The samples represent the entire SGC population in Finland from 1991-1996. Mortality follow-up ended December 31, 2006. RESULTS: The study population of 107 patients consisted of 47 male and 60 female subjects, ranging in age at the time of diagnosis between 23 and 90 years. The minimum follow-up time was 10.6 years and the maximum 15.9 years. By age-adjusted analysis lower staining intensity was associated with worse overall survival of patients with acinic cell carcinoma (p = 0.047, HR 6.5, 95% Cl 1.0-41.7) and in mucoepidermoid carcinoma (p = 0.010, HR 9.3, 95% CI 1.7-50.0). Low staining intensity was also associated with worse disease-specific survival of patients with acinic cell carcinoma (0-1 vs. 2-3; p = 0.047, HR 13.7, 1.0-200.0). VCI Ki-67 was an important prognostic factor for survival of the entire data set (p < 0.0001, HR 4.7, 95% Cl 2.3-9.8). CONCLUSIONS: MMP-7 is associated with the prognosis of patients with acinic cell and mucoepidermoid carcinoma.

Ki-67 proliferation rate as a prognostic marker in major salivary gland carcinomas.

OBJECTIVES: The study was performed to evaluate the prognostic relevance of cell proliferation associated with Ki-67/ Mib-1 immunostaining in malignant tumors of the major salivary glands. METHODS: Cell proliferation was evaluated by Mib-1 antibody against Ki-67 antigen in 41 patients with cancer of the parotid or submandibular glands, including 14 acinic cell carcinomas, 12 ductal carcinomas, 7 mucoepidermoid carcinomas, 5 carcinomas ex pleomorphic adenoma, 1 adenoid cystic carcinoma, 1 undifferentiated carcinoma, and 1 polymorphous low-grade adenocarcinoma. RESULTS: Patients with Ki-67 values of more than 15% and those with Ki-67 values of 15% or less differed both in disease-free survival (p < 0.001) and in overall survival (p < 0.001). We evaluated the association between Ki-67 and time to recurrence in correlation to age, sex, ductal histotype, and N stage; the Cox regression model was significant (p = 0.013). In the group of patients with T1 and T2 cancers, those with Ki-67 values of 15% or less had better survival rates than did those with Ki-67 values of more than 15% (p = 0.004). In the group of patients with N0 cancers, those with Ki-67 values of 15% or less had a better survival than did those with Ki-67 values of more than 15% (p < 0.001). CONCLUSIONS: To our knowledge, this is the first study to stratify different risk classes in early T1-T2 or N0 malignant tumors of the major salivary glands that identified aggressive lesions with elevated Ki-67 expression at an initial stage.

Pancreatic acinar cell carcinomas and mixed acinar-neuroendocrine carcinomas are more clinically aggressive than grade 1 pancreatic neuroendocrine tumours.

Acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MAcNECs) of the pancreas are extremely rare carcinomas with a significant component with acinar differentiation. To date, the clinicopathological behaviours of these neoplasms remain unclear. In this study, we evaluated the histopathological and molecular characteristics of 20 ACCs and 13 MAcNECs and compared them to a cohort of 269 well-differentiated pancreatic neuroendocrine tumours (PanNETs). Compared to PanNETs, both ACCs and MAcNECs had an advanced pT classification (p<0.001), as well as more prevalent lymphovascular and perineural invasion (p=0.002) and lymph node and distant metastases (p<0.001). Patients with MAcNECs had worse overall (p<0.001) and recurrence-free survival (p<0.001) than those with PanNETs, but no significant difference with those with ACCs. Subgroup analyses revealed that patients with ACCs and MAcNECs had significantly worse recurrence-free survival than those with grade 1 PanNET (p<0.001), and patients with MAcNECs also had worse overall survival than those with grade 1 and 2 PanNETs (p<0.001, and p=0.001). ACCs presented more commonly with intraductal growth (p=0.014) than MAcNECs, while MAcNECs more often had lymph node metastasis (p=0.012) than ACCs. The telomere maintenance mechanism Alternative Lengthening of Telomeres (ALT) was assessed by telomere-specific FISH, and ALT was detected in 1 of 20 ACCs and in three of the 13 MAcNECs. Patients with MAcNECs and ACCs had worse survival and more aggressive behaviour than those with grade 1 PanNETs; thus, the clinicopathological behaviour of MAcNECs resembles ACCs rather than PanNETs. Combined neuroendocrine and acinar cell immunohistochemical markers are helpful for differentiating these different tumour types.

The contemporary trend in worsening prognosis of pancreatic acinar cell carcinoma: A population-based study.

BACKGROUND: Primary acinar cell carcinoma (ACC) is a rare exocrine tumor of the pancreas with unclear clinical characteristics. Our goal was to determine the incidence and update the clinical characteristics and outcomes of ACC. METHODS: Through the Surveillance, Epidemiology, and End Results (SEER) database, we identified 252 patients with the latest diagnosis of ACC (2004-2016). The age-adjusted incidence (AAI) was calculated using the SEER*Stat Software version 8.3.6. The Kaplan-Meier method was used to draw survival curves and differences among them were compared by the log-rank test. Cox proportional hazards models were used to evaluate factors that had independent predictive effects on the overall survival. RESULTS: The AAI of pancreatic ACC was on the rise with the mean age at diagnosis of 63.79±14.79 years. Most patients (15.9%) had poorer differentiated tumors. The patients presented with distant stage were 54.4% compared with 53.1% between 1988 and 2003. The 1-, 2-, and 5-years survival rates for pancreatic ACC patients were 53.5%, 34.6%,17.5%, respectively (compared with 78.5%, 67.0%, and 42.8%, between 1988 and 2003). The multivariate COX analysis showed that the patient's age, surgery, chemotherapy, and summary stage, but not marital status were independent prognosis factors for ACC. CONCLUSIONS: Pancreatic ACC is a highly malignant tumor with an increasing incidence in recent years. The rate of distant metastasis is increasing and the survival rate is worse than in the past, suggesting that it may require more aggressive treatment and follow-up. Surgery, radiotherapy, and chemotherapy are all effective treatments, but prospective studies are still needed to verify them.