Poorly-differentiated Adenocarcinoma Research Articles

Retraction Note: Urachal tumour: case report of a poorly understood carcinoma

Urachal carcinoma is an uncommon neoplasm associated with poor prognosis. A 45-year-old man was admitted with complaints of abdominal pain and pollakisuria. A soft mass was palpable under his navel. TC-scan revealed a 11 × 6 cm tumor, which was composed of a cystic lesion arising from the urachus and a solid mass component at the urinary bladder dome. The tumor was removed surgically. Histological examination detected poor-differentiated adenocarcinoma, which had invaded the urinary bladder. The patient has been followed up without recurrence for 6 months. The urachus is the embryological remnant of urogenital sinus and allantois. Involution usually happens before birth and urachus is present as a median umbilical ligament. The pathogenesis of urachal tumours is not fully understood. Surgery is the treatment of choice and role of adjuvant treatment is not clearly understood.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom.

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

Abstract PO023: Preliminary data on metformin therapy in DICER1-deleted endometrial cancer

Abstract We created and characterized the first genetically engineered mouse model of poorly-differentiated endometrial adenocarcinoma (dcKO, PgrCre; Ptenflox/flox; Dicer1flox/flox). As an additional novel model system, using CRISPR-Cas9, we created and characterized an isogenic cell line with the deletion of DICER1 (DICER1−/− Ishikawa cells). Transcriptomic profiling across mouse and human models revealed activated pathways, including AMP kinase and insulin signaling. Ingenuity Pathway Analysis revealed metformin as a likely therapeutic target. Previous studies have suggested that metformin may be useful for preventing and treating endometrial cancer in women. However, recent clinical trials showed combined treatment of metformin with paclitaxel and carboplatin was not significantly associated with increased progression-free survival or overall survival for advanced or recurrent endometrial cancer. To test the effects of metformin in our mouse model, female mice received ad lib water containing metformin (5 mg/mL) or water beginning at weaning. Survival studies showed worse survival for well-differentiated endometrial adenocarcinoma (Pten cKO, PgrCre; Ptenflox/flox; Dicer1+/+) with treatment with metformin (P=0.007), while there was no difference for dcKO mice treated with metformin. Similarly, in vitro studies showed that the treatment of DICER1−/− Ishikawa cells treated with metformin did not affect cellular proliferation. Our in vivo and in vitro model systems represent important tools to study metformin and other therapeutics for rare yet aggressive endometrial cancers. Citation Format: Xiyin Wang, Robert Emerson, Russell Broaddus, John Lydon, Francesco DeMayo, Shannon M. Hawkins. Preliminary data on metformin therapy in DICER1-deleted endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO023.

S1656 Not Your Standard Adenocarcinoma, a Case of Medullary Carcinoma of the Colon

INTRODUCTION: Adenocarcinoma of the colon is the most common type of colon cancer. Medullary carcinoma (MC) of the colon is a rare histological subtype of adenocarcinoma. MC has been described to have specific histopathological features but can still be difficult to distinguish from poorly differentiated adenocarcinoma. We aim in this case report to shed light on this rare subtype of colon cancer and describe its histopathological features. CASE DESCRIPTION/METHODS: 76-year-old male presented to our hospital reporting 3 months of back pain, fatigue, and 10lb weight loss. Past medical history significant for atrial fibrillation and history of renal cell carcinoma. CT abdomen/pelvis showed a necrotic mass within the ascending colon suggestive of colon cancer. Metastatic lymph nodes were also suspected on the scan. Subsequent colonoscopy showed a large mass at the hepatic flexure. Multiple biopsies were taken from mass. Histopathologic sections showed sheets of malignant epithelial cells extending from the submucosa into the lamina propria. Immunohistochemical staining demonstrated that the malignant cells were positive for pan-cytokeratin, but negative for CK20, CDX2, S-100, CD45, synaptophysin, chromogranin, and PSA. These initial findings were consistent with invasive poorly differentiated carcinoma. Further immunohistochemical testing was done and showed mismatch repair deficiency with loss of MLH1 and PMS2 consistent with medullary carcinoma of the colon, which typically shows aberrant loss of CK20 and CDX2 (typical markers of colorectal adenocarcinoma). Due to patients advanced disease (stage IV), decision made to start palliative chemotherapy with Xeloda + Oxaliplatin + Avastin. Patient passed away approximately three months after initial diagnosis. DISCUSSION: MC of the colon is extremely rare with limited clinical and epidemiologic data. Based on population-based analysis, medullary carcinoma makes up 5-8 cases for every 10,000 colon cancers diagnosed. Most patients are diagnosed earlier in the disease course and metastatic disease is seen in 10% of patients at time of diagnosis. Immunohistochemical analysis is essential to differentiate from poorly-differentiated and undifferentiated colon adenocarcinomas. Classic findings include loss of staining for MLH-1 and CDX-2. In the current published data, overall prognosis of MC is favorable when compared to poorly differentiated or undifferentiated adenocarcinomas. However, data is limited regarding available treatment strategies and response.Figure 1

S1533 An Unusual Presentation of a Rare Ampullary Neoplasia

INTRODUCTION: Ampullary neoplasias are uncommon, with most tumors being of pancreaticobiliary or intestinal origins. SRCC of the Ampulla of Vater is an extremely rare variant of adenocarcinoma with only 38 previously cases reported in the literature. Little is known about the pathogenesis, treatment, and outcomes of this uncommon subtype. We report a case of ampullary SRCC in a patient who presented with a TIA and choledocholithiasis. CASE DESCRIPTION/METHODS: An 83-year-old lady was brought to the hospital with one day of slurred speech and right-sided weakness. Stroke workup was negative, her symptoms resolved rapidly, and she was diagnosed with a TIA. GI service was consulted for elevated liver enzymes. Patient reported decreased appetite for a few weeks with some weight loss. Denied fevers, chills, nausea, vomiting, jaundice, pruritis, dark urine, pale stools, new medications, alcohol abuse, or Tylenol use. She was a 15-pack year active smoker. On exam, she was afebrile with stable vitals and mild epigastric tenderness. Lab work up showed WBC 15.9 with a left shift. CMP noted TBili 3.6 (Conjugated 1.4), AST 442, ALT 260, ALP 645, Lipase 57. RUQ US showed cholelithiasis and a dilated CBD (7.3 mm). MRCP revealed mild diffuse intrahepatic and extrahepatic biliary dilatation, multiple small stones within a 1.6cm CBD with appropriate tapering at the ampulla. ERCP revealed 2-3 cm nodular cratered ulceration with irregular heaped up margins adjacent to the Ampulla of Vater. Patient underwent papillotomy, stone extraction, and placement of a fully covered wall stent. Tumor markers noted CA19-9 of 50. Pathology showed infiltrating poorly-differentiated adenocarcinoma with signet-ring cell features of the Ampulla of Vater. Tumor cells were positive for CK7, CK19, CK20, CDX2, pan keratin, MUC-1, MUC-2; and negative for MUC-6 by immunohistochemistry (IHC). After extensive discussion of findings, treatments options with multidisciplinary team including surgical oncology and palliative care services, patient declined surgical intervention and decided to spend her remaining days at home. DISCUSSION: A signet-ring variant of the adenocarcinoma of the Ampulla of Vater is an extremely rare neoplasm. This is a unique case of a lady with concomitant choledocholithiasis incidentally found to have SRCC of the Ampulla of Vater. Given the rarity of these cases, special staining and IHC will add to our knowledge of the origins of these neoplastic cells and help tailor future therapeutics.Figure 1.: Histological examination of biopsied specimen in high power view showing atypical infiltrating cells with eccentric nuclei and intra-cytoplasmic mucin.Figure 2.: Histological examination showing adenocarcinoma with characteristic signet ring cells.Figure 3.: Histological examination at lower power with signet ring cell adenocarcinoma tumor infiltration.

Impact of sex and histology on the therapeutic effects of fluoropyrimidines and oxaliplatin plus bevacizumab for patients with metastatic colorectal cancer in the SOFT trial.

Mechanisms accounting for sex differences in the incidence of adverse events caused by fluoropyrimidine treatments, and histologic differences in efficacy are insufficiently understood. We determined differences between the sexes in terms of the safety of S-1 plus oxaliplatin (SOX)/bevacizumab-versus-l-leucovorin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX)/bevacizumab, and the impact of histology on their therapeutic effects, in 512 unresectable metastatic colorectal cancer patients from the SOFT phase III study. Nausea (OR: 2.88, P < 0.001) and vomiting (OR: 3.04, P = 0.005) occurred more frequently in females than males treated with SOX/bevacizumab, while nausea (OR: 2.12, P = 0.006), vomiting (OR: 3.26, P = 0.004), leukopenia (OR: 2.61, P < 0.001), neutropenia (OR: 2.92, P < 0.001), and alopecia (OR: 4.13, P < 0.001) were higher in females on FOLFOX/bevacizumab. Mean relative dose intensities (RDIs) of S-1 during all cycles of SOX/bevacizumab were significantly lower in females (73.9%) than males (81.5%) (P < 0.001), while RDIs of continuous infusion of 5-FU in the FOLFOX/bevacizumab regimen were 75.0% in females and 80.5% in males (P = 0.005). No significant differences in efficacy with regard to overall survival (OS) and progression-free survival (PFS) were identified between the sexes for either SOX/bevacizumab or FOLFOX/bevacizumab treatment. Patients with poorly-differentiated adenocarcinoma had significantly worse OS (HR: 2.72, 95% CI: 1.67-4.44, P < 0.0001) and PFS (HR: 1.89, 95% CI: 1.18-3.02, P = 0.0079) than patients with well- or moderately-differentiated adenocarcinoma. Female patients experienced more frequent and severe adverse reactions to SOX/bevacizumab and FOLFOX/bevacizumab and a worse prognosis for poorly-differentiated adenocarcinoma were confirmed in this phase III study. This warrants further translational research to identify the responsible mechanisms.

Clinical impact of non-predominant histopathological subtypes on the long-term prognosis of colorectal cancer patients in Japan.

We performed a retrospective study to clarify the long-term prognosis of patients with histopathological high-grade colorectal cancer (CRC). We reviewed data from 24 institutions for 18,360 patients with pStage I to III CRC who had undergone curative surgery between 2004 and 2012. The patients were classified into seven groups according to the proportion of the histopathological component: classical adenocarcinoma (CAC) group, M-l and M-h groups (< 50% and ≥ 50% mucinous adenocarcinoma, respectively), P-l and P-h groups (< 50% and ≥ 50% poorly differentiated adenocarcinoma, respectively), and S-l and S-h groups (< 50% and ≥ 50% signet-ring cell carcinoma (SRCC), respectively). The 5-year recurrence-free survival (RFS) rates of the M-l, P-l, and S-l groups were 75.5%, 68.4%, and 52.4%, respectively, and were significantly lower than those of the CAC group (83.5%, hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01-1.48, p = 0.0365; HR 1.60, 95% CI 1.32-1.91, p < 0.0001; HR 2.61, 95% CI 1.30-4.57, p = 0.0090, respectively). The 5-year RFS of the P-l and S-l groups was as poor as that of the P-h and S-h groups, respectively (HR 0.87, 95% CI 0.68-1.10, p = 0.25; HR 0.90, 95% CI 0.37-2.13, p = 0.81, respectively). The histopathological component of the S-l group was an independent factor affecting overall survival in multivariate analysis. The long-term prognoses of the non-predominant poorly differentiated adenocarcinoma (PAC) groups were as poor as those of the predominant group. In particular, the histopathological component of the P-l and S-l groups could be classified into predominant PAC and SRCC subtypes for appropriate prognostic predictions.

Diagnostic Findings of Sclerosing Mesenteritis and the Disease Correlations with Caecal Adenocarcinoma

Sclerosing mesenteritis (SM) is a rare disease with non-specific clinical manifestations and should be supported by radiological examination and confirmed by histopathological evaluation. Its relationship with cancer especially caecal adenocarcinoma is still unclear. This case report describes a young man who was diagnosed as having SM and poorly-differentiated caecal adenocarcinoma.

Structural and functional indicators of erythrocyte membranes in gastric cancer patients with different histotypes of the tumor and stages of the malignant process

The purpose was to study the structural and functional parameters of erythrocyte membranes in the blood of patients with gastric cancer (GC) – adenocarcinoma, depending on its grade, signet ring cell carcinoma (SRCC), and combined gastric lesions (CGL). Materials and methods . The membrane fluidity in the area of the lipid bilayer and protein-lipid contacts, the polarity of the lipid bilayer and the immersion of proteins in the lipid matrix of the membrane in red blood cells were evaluated by fluorimetry using the hydrophobic pyrene-based probe. The study included 86 patients with GC divided into six groups: well- and moderately-differentiated adenocarcinoma (G1-2); poorly-differentiated adenocarcinoma (G3); SRCC; CGL and two groups of patients with a component of undifferentiated cancer: G4 + SRCC and G4 + G2-3. The results of the study were also analyzed in patients with serosal invasion and the spread to adjacent structures (T4 according to the TNM classification of malignant tumors) and in patients with stage IV disease. Results. In all groups of GC patients, an increase in the membrane fluidity was observed. It was more pronounced in the zone of protein-lipid contacts, but it was also observed in the lipid bilayer. The membrane fluidity increased together with the grade of adenocarcinoma and was maximal when there were undifferentiated cells in stomach tumors, reaching 93.8% in the zone of protein-lipid contacts and 54.1% in the lipid bilayer, compared with healthy people (20 donors). An increase in the polarity of the lipid phase was also observed; it was most pronounced (by 7–8%, p = 0.002–0.003) in adenocarcinoma patients with undifferentiated cells and with stage IV disease. A change in the immersion of proteins in the lipid matrix of erythrocytes was less characteristic of GC, compared with other cancers (breast, lung tumors, gynecological oncopathology, etc.). Conclusions. Changes in the structural and functional properties of erythrocyte membranes reflect the state of the disease in patients with gastric cancer and may be important for predicting the course of the disease and the success of treatment.

BMI-adjusted prognosis of signet ring cell carcinoma in patients undergoing radical gastrectomy for gastric adenocarcinoma

BackgroundCompared with other histologic types, signet ring cell gastric carcinoma (SRC) has unique oncological characteristics, and its implication on the prognosis of gastric cancer patients remains unclear. The purpose of this study was to evaluate the prognostic impact of body mass index (BMI) on SRC patients. MethodsA retrospective analysis was performed using the clinical records of 3342 patients with SRC or tubular adenocarcinoma who underwent radical gastrectomy between 2000 and 2014. Patients were divided into three groups according to histologic subtype: SRC, well-to-moderately differentiated adenocarcinoma (WMD), and poorly differentiated adenocarcinoma (PD). We compared the survival of SRC patients with that of tubular adenocarcinoma patients according to BMI. ResultsThe 5-year survival of SRC was significantly worse than that of WMD (P < 0.001) but superior to that of PD (P < 0.001). BMI-stratified analysis showed that in the high-BMI group, the prognosis of SRC was similar to that of WMD (P > 0.05) and better than that of PD (P < 0.001). In normal-BMI patients, SRC had a worse prognosis than WMD (P < 0.001) but a more favorable prognosis than PD (P < 0.001). SRC among low-BMI patients displayed much poorer survival than did both WMD (P < 0.001) and PD (P = 0.005). Multivariate analysis indicated that the risk of death was the lowest in SRC patients with a high BMI and highest for SRC patients with a low BMI (low-BMI hazard ratio: SRC 1 vs. WMD 0.51 and PD 0.53). ConclusionSRC has worse prognostic impact as BMI decreases. BMI leads to differing prognosis of SRC compared with tubular adenocarcinoma.

Deep-Hipo: Multi-scale receptive field deep learning for histopathological image analysis.

Digitizing whole-slide imaging in digital pathology has led to the advancement of computer-aided tissue examination using machine learning techniques, especially convolutional neural networks. A number of convolutional neural network-based methodologies have been proposed to accurately analyze histopathological images for cancer detection, risk prediction, and cancer subtype classification. Most existing methods have conducted patch-based examinations, due to the extremely large size of histopathological images. However, patches of a small window often do not contain sufficient information or patterns for the tasks of interest. It corresponds that pathologists also examine tissues at various magnification levels, while checking complex morphological patterns in a microscope. We propose a novel multi-task based deep learning model for HIstoPatholOgy (named Deep-Hipo) that takes multi-scale patches simultaneously for accurate histopathological image analysis. Deep-Hipo extracts two patches of the same size in both high and low magnification levels, and captures complex morphological patterns in both large and small receptive fields of a whole-slide image. Deep-Hipo has outperformed the current state-of-the-art deep learning methods. We assessed the proposed method in various types of whole-slide images of the stomach: well-differentiated, moderately-differentiated, and poorly-differentiated adenocarcinoma; poorly cohesive carcinoma, including signet-ring cell features; and normal gastric mucosa. The optimally trained model was also applied to histopathological images of The Cancer Genome Atlas (TCGA), Stomach Adenocarcinoma (TCGA-STAD) and TCGA Colon Adenocarcinoma (TCGA-COAD), which show similar pathological patterns with gastric carcinoma, and the experimental results were clinically verified by a pathologist. The source code of Deep-Hipo is publicly available athttp://dataxlab.org/deep-hipo.

2020 challenges in diagnosis and staging of lung cancer

Pathology plays an important role in diagnosis and management of patients with non-small cell lung carcinoma (NSCLC). The current (2015) WHO classification of lung tumours includes histologic and immunophenotypic (IHC) criteria. Adenocarcinomas are the primary focus of shifting nomenclature, emphasising histologic patterns with clinical and biological relevance. Minimally invasive and lepidic-predominant non-mucinous adenocarcinomas represent well-differentiated tumours, while solid and/or micropapillary growth patterns signify poorly-differentiated adenocarcinomas. Poorly-differentiated carcinomas that cannot be classified on the basis of histology alone can instead be subclassified using a limited IHC panel targeting TTF-1 and p63/p40. For adenocarcinomas with non-invasive (lepidic) components, pT staging hinges on the size and extent of only the invasive component. Multifocal tumours are staged based on a combination of gross growth characteristics and histologic findings. Pathology’s role extends beyond diagnosis and staging in response to expectations that cells and tissues will be available for expanded biomarker testing in patients with advanced stage disease. Testing strategies for predictive biomarkers frequently include a combination of immunohistochemistry and increasingly comprehensive molecular profiling as single gene assays become less common. Panels are constructed to balance the number of actionable targets over and against our ability to test extremely small amounts of viable tumour.

Solid-type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex.

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer.

The incidence of prostate cancer (PCa) is increasing, and it is currently the second most frequent cause of death by cancer in men. Despite advancements in cancer therapies, new therapeutic approaches are still needed for treatment-refractory advanced metastatic PCa. Cross-species analysis presents a robust strategy for the discovery of new potential therapeutic targets. This strategy involves the integration of genomic data from genetically engineered mouse models (GEMMs) and human PCa datasets. Considering the role of antioxidant pathways in tumor initiation and progression, we searched oxidative stress-related genes for a potential therapeutic target for PCa. First, we analyzed RNA-sequencing data from Pb-Cre4; Ptenf/f mice and discovered an increase in sulfiredoxin (Srxn1) mRNA expression in high-grade prostatic intraepithelial neoplasia (PIN), well-differentiated adenocarcinoma (medium-stage tumors), and poor-differentiated adenocarcinoma (advanced-stage prostate tumors). The increase of SRXN1 protein expression was confirmed by immunohistochemistry in mouse prostate tumor paraffin samples. Analyses of human databases and prostate tissue microarrays demonstrated that SRXN1 is overexpressed in a subset of high-grade prostate tumors and correlates with aggressive PCa with worse prognosis and decreased survival. Analyses in vitro showed that SRXN1 expression is also higher in most PCa cell lines compared to normal cell lines. Furthermore, siRNA-mediated downregulation of SRXN1 led to decreased viability of PCa cells LNCaP. In conclusion, we identified the antioxidant enzyme SRXN1 as a potential therapeutic target for PCa. Our results suggest that the use of specific SRXN1 inhibitors may be an effective strategy for the adjuvant treatment of castration-resistant PCa with SRXN1 overexpression.

Expression of Integrin-linked Kinase in Gastric Cancer and Its Relationship with Clinicopathological Characteristics

Objective: To explore the value of integrin-linked kinase (ILK) in the diagnosis of gastric cancer, its mechanism of action in the pathogenesis and its influence on tumor metastasis. Methods: Collect 100 cases of gastric cancer diagnosed pathologically, detect the positive expression of ILK, and analyze its biological characteristics. Results: The positive rate of ILK in gastric cancer tissue (57.0%) is significantly higher than that in the control group (12%), and the positive rate of ILK gradually increased with the progress of superficial gastritis, chronic atrophic gastritis with atypical hyperplasia and gastric cancer. The differences between the four groups are statistically significant. There is a significant difference in the positive rate of ILK among well-differentiated, moderately-differentiated, poorly-differentiated and undifferentiated adenocarcinomas (P<0.001). The positive rate (25%) of ILK in the uninvaded serosal layer (T1+T2) is significantly lower than the positive rate (75.0%) in the invaded serosal layer (T3+T4). There is a significant difference in the positive rate of ILK in stage I, II, III and IV (P<0.001). In the localized type (I+II), the positive rate of ILK (24.39%) is significantly lower than that of the invasive type (III+IV) (79.66%). The positive rate of ILK in patients without lymph node metastasis (30.23%) is significantly lower than that of patients with lymph node metastasis (77.19%). Conclusion: The positive rate of ILK in gastric cancer tissue is significantly higher than that in adjacent tissues. The higher the positive rate, the worse the prognosis. ILK is an independent risk factor affecting the prognosis of patients.

Immunoexpression of Matrix Metalloproteinase-9 in Colorectal Adenocarcinoma

Colorectal carcinoma is one of the most common malignant tumors of gastrointestinal tract and is a contributing factor of cancer mortality in Myanmar. Matrix metalloproteinase-9 is a proteolytic enzyme which breaks down extracellular matrix leading to tumor progression, contri-buting as a potential prognostic marker nowadays. The study was aimed to determine MMP-9 immunoexpression in colorectal adenocarcinoma and its association with Astler-Coller staging. A cross-sectional descrip-tive study was done on 42 specimens of colorectal adenocarcinoma. All tissue specimens were studied with haematoxylin and eosin to categorize histological types and grades. Out of 42 cases, 21.4% were well differentiated, 57.2% were moderately differentiated and 21.4% were poorly differentiated. According to Astler-Coller staging, 11.9% were found to be in stage B1, 40.5% in stage B2, 7.1% in stage C1, 33.3% in stage C2 and 7.1% in stage D. 81% (34/42) of colorectal carcinoma showed positive MMP-9 immunoexpression. Positive MMP-9 immuno-expression was seen in 91% of conventional adenocarcinoma, 40% of mucinous carcinoma and no cases signet ring carcinoma. The findings of the study pointed out that MMP-9 immunoexpression was positively associated with histological types of colorectal adenocarcinoma (p=0.001). MMP-9 immunoexpression was positive in 88.9% of well differentiated adenocarcinoma, 91.7% of moderately differentiated adenocarcinoma and 44.4% of poorly-differentiated adenocarcinoma (p=0.007). Regarding the immunoexpression of MMP-9 in different Astler-Coller staging, positive MMP-9 immunoexpression was seen in 60% of the cases in stage B1, 76.5% in stage B2, 66.7% in stage C1, 92.9% in stage C2 and 100% in stage D. The findings of the study can be extrapolated to predict prognosis and help in better management of colorectal adenocarcinoma by introducing targeted therapy against MMP-9 in future.

Frequency of HER2/neu over expression in adenocarcinoma of the gastrointestinal system, a Study of 70 cases

Aim: To study the frequency of HER2/neu overexpression in esophageal, gastric, small intestine and colorectal adenocarcinomas, to study the association of HER2/ neu overexpression with histopathological differentiation of esophagus, stomach, small intestine and colorectal adenocarcinomas and identifying its significance. Materials and Methods: Cross sectional study was performed on 70 cases which include resected specimens of stomach, small intestine and colorectal adenocarcinoma and biopsies of esophagus and these organs. The samples were divided into Group A (Esophagus and stomach) and Group B (Small intestine and colorectal). The samples were grossed and processed in the pathology department, and sections were stained with hematoxylin and eosin stain for histopathological confirmation of malignancy and graded as well-differentiated (gradeI), moderately-differentiated (grade II) and poorly-differentiated (gradeIII ) adenocarcinomas. The confirmed samples were processed for immunomarker study of HER2/ neu. Results: Over expression of HER2/ neu was found in 17(24.3 %) patients overall. Out of 17 HER2/ neu positive cases, 4(26.7%) were from group a, while 13(23.6%) were from group b. No staining or membrane staining in score “0” and considered negative for HER2/ neu overexpression. Faint/barely perceptible membranous staining in 10% of tumors cells were observed in 5 (7.1 %) patie nts, which were labeled as score “1” and considered negative. Weak to moderate complete, basolateral or lateral membranous staining in 10% tumor cells were observed in 2(2.9%) patients, which were labeled as score “2” and considered equivocal. Strong complete, basolateral or lateral membranous staining in 10% of tumors cells were observed in 17(24.3%) patients, which were labeled as score “3” and considered positive. Out of 70 patients, 37(52.9%) were suffering from grade-II malignancy, 17 (24.3 %) from grade- I and 16 (22.8%) from grade-III. According to histologic

1349 A Rare Presentation of Cholecystogastric Fistula With Associated Mirizzi Syndrome Leading to the Diagnosis of Gallbladder Cancer

INTRODUCTION: Biliary fistulas are a rare complication of gallstone disease. Technological advances have allowed for successful management &amp; diagnosis. Mirizzi syndrome is a condition seen in less than 1% of patients with cholelithiasis &amp; malignancy in 5 to 28% of cases. This is a rare presentation of coexistent Mirizzi syndrome and a cholecystogastric fistula leading to the diagnosis of gallbladder adenocarcinoma. CASE DESCRIPTION/METHODS: A 68 y/o female presented to the ER with complaints of jaundice &amp; pruritis. Records demonstrated prior CTA&amp;P with cholelithiasis with stranding &amp; nonspecific stranding around the distal stomach. MRI w/wo contrast demonstrated loss of fat plane between gallbladder &amp; stomach suggestive of fistulizing disease &amp; a filling defect within the extrahepatic common hepatic duct related to external compression suggestive of Mirizzi Syndrome, no pneumobilia was seen. EGD/EUS was without direct visualization a fistulous tract, but revealed ulceration of gastric mucosa suggesting extrinsic pressure from a gallstone. ERCP demonstrated a stricture within the proximal CBD. Brushings were negative for malignancy. Lap chole revealed adherence of the stomach to the gallbladder fundus &amp; takedown of cholecystogastric fistula was also performed. Histology from gallbladder specimen returned positive for invasive poorly-differentiated adenocarcinoma with transmural and lymphatic invasion. DISCUSSION: The presentation of cholecystogastric fistula generally includes pneumobilia &amp; lacks pruritis suggestive of obstructive jaundice due to drainage of the biliary system via tract formation. Yet during the development of the fistulous tract the presentation varies quite drastically. Surgery is guided by the sub-classification of fistula formation/erosion as noted in the table figure. ERCP allows better characterization of the anatomy, in addition to offering the potential for therapeutic intervention with biliary decompression. There is an important known relationship between Mirizzi syndrome &amp; gallbladder cancer likely related to the recurrent irritation occurring in the region along with chronic biliary stasis therefore frozen sections should be performed in all cases of Mirizzi syndrome to conclusively evaluate for gallbladder cancer. Our case highlights the malignancy potential within the presentation of fistulizing gallbladder disease. With a heightened index of suspicion and advancements in endoscopic and surgical techniques management of these patients will hopefully become less challenging.

Clinicopathological features and prognostic analysis of signet ring cell gastric carcinoma: a population-based study

Background: The impact of signet ring cell carcinoma (SRC) on gastric cancer patients’ prognosis remains controversial. The aim of this study was to evaluate the clinicopathological characteristics and prognosis of SRC carcinoma and adenocarcinoma (AC) in patients with gastric cancer (GC). Methods: An electronic search of SRC and AC cases from 2004 to 2015 was conducted within the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. According to histological type, AC patients were divided into two groups: well- and moderately differentiated (WMD) and, poorly differentiated adenocarcinoma (PD). Kaplan-Meier (KM) curves were used to compare 5-year overall survival (OS), Univariate, and multivariable analysis were performed by Cox regression model. Results: We identified 29,851 gastric cancer patients, among whom 16,482 were in the M0 group and 13,369 were in the M1 group. SRC patients had younger age distribution and were more seen in women. SRC was more likely to be found in advanced T and N stage, and with more distant metastasis. The most common metastatic site was bone-in SRC, while the most common site was the liver for WMD and PD. In the M0 group, multivariable analyses demonstrated that SRC had a similar survival rate with WMD and PD in stage I, and with the stage increasing, the overall survival of SRC was worse than that of WMD. Meanwhile, in the M1 group, SRC had an even worse prognosis than PD. Conclusions: SRC was significantly different from AC in its clinicopathologic characteristics. Although the prognosis of SRC was similar to AC in the early stage, it had a more inferior prognostic impact with the progression of the disease. Different therapeutic regimens and imaging evaluations should be applied according to the histological types of gastric cancer.