scholarly journals The Clinicopathological Characteristics and Prognoses of dMMR Gastric Adenocarcinoma Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jie Wang ◽  
Yanfeng Xi ◽  
Jian Zhao ◽  
Xuetong Rong ◽  
Weidong Lu ◽  
...  

Background. Few studies on the clinicopathological features and prognosis of DNA mismatch repair deficiency (dMMR) gastric cancer (GC) have been reported, and no clear conclusions have been drawn about the factors affecting the prognosis of dMMR GC. The aim of this study was to explore the clinicopathological characteristics and prognoses of dMMR GC patients. Methods. From May 2011 to November 2020, GC patients who underwent surgery with dMMR confirmed by immunohistochemistry (IHC) at the Affiliated Cancer Hospital of Shanxi Medical University were selected. The patients’ clinical and pathological data were collected. The recurrence-free survival (RFS) and overall survival (OS) rates of the patients were determined through follow-up. SPSS 26.0 was used to analyze the patients’ clinicopathological features and prognoses. Results. A total of 162 dMMR GC patients met the inclusion criteria, and the median age was 63.5 years (32–89 years). dMMR GC was more common in males (65% vs. 35%), and most of the cases were stage II (the prevalence of stage I was 22%, that of stage II was 43%, that of stage III was 30%, and that of stage IV was 5%). Most of the lesions were located in the antrum (49%), followed by the cardia (25%). PMS2 and MLH1 (57%) deficiency was most common. Kaplan–Meier analysis showed that factors related to OS were family history ( P = 0.048 ), number of lymph node (LN) metastases ( P < 0.001 ), vascular tumor thrombus ( P < 0.001 ), HER2 expression status ( P = 0.025 ), and clinical stage ( P < 0.001 ). The factors related to RFS included vascular tumor thrombus ( P < 0.001 ), number of LN metastases ( P < 0.001 ), and clinical stage ( P < 0.001 ). Conclusion. In this study, dMMR GC was more common in men, and the median age was 63.5 years. Most of the lesions were in the antrum and showed the combined deletion of MLH1 and PMS2. dMMR GC patients tended to be early stage, and the prognosis of those with early-stage GC was better. dMMR GC patients with vascular tumor thrombus or >6 LN metastases had a high recurrence rate and poor survival outcome.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5330-5330 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Dai Chihara ◽  
Naoko Asano ◽  
Ken Ohmachi ◽  
Tomohiro Kinoshita ◽  
...  

Abstract [Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the overexpression of cyclin D1 derived from t(11;14)(q13;q32) and poor prognosis. Most MCLs show nodal presentation, but also accompany extranodal involvement, such as bone marrow, peripheral blood or gastrointestinal tract. As a result, many MCLs present with advanced stage disease. Since only a small portion of patients show limited-stage disease, minimal data exist on treatment of patients diagnosed with limited stage disease. Nevertheless, the treatment strategy of MCL is recommended according to the clinical stage of limited- (stage I or non-bulky II) vs. advanced-stage, as well as other types of lymphoma. [Patients and methods] We recently collected 633 patient data of MCL (Chihara, et al. Ann Oncol 2015). Information of clinical stage was available in 626 patients. The patient data were retrospectively analyzed the by the clinical stage at initial presentation. [Results] The clinical stage was I in 24 patients (4%), II in 33 (5%), III in 70 (11%), and IV in 499 (80%). Only one patient presented with bulky stage II. Detailed demographic information by the clinical stage are listed in Table. Age and sex were not significantly different by clinical stage. Limited stage patients were associated with better performance status (PS), less B symptoms, no extranodal involvement, and lower lactate dehydrogenase (LDH) level and white blood cell (WBC) count. Most patients in any stage were treated with cytotoxic chemotherapy, but more patients in limited stage received radiotherapy. The proportion of high-dose cytarabine (HDCA)-containing regimen over CHOP/CHOP-like was higher in advanced stage patients. Complete and overall response rates were 92% and 96% in stage I, 58% and 94% in stage II, 66% and 86% in stage III, and 52% and 82% in stage IV, respectively (P = 0.02). However, the higher response rate in limited stage patients did not translate into better prognosis. The median survival was 11.0 years in stage I, 13.4 years in stage II, 11.5 years in stage III, and 5.6 years in stage IV (Figure). The prognosis was not significantly different among patients with stage I, II, and III (P = 0.33). [Conclusion] Prognosis of limited-stage MCL was almost similar to that of stage III MCL. Although the present study includes several limitations including a retrospective nature and limited number of patients, prognosis of patients with limited-stage MCL was not satisfactory. The significance of radiotherapy, as well as the optimal choice of chemotherapy, for limited-stage MCL needs re-evaluation. Table Table. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Kyowa Hakko kirin: Honoraria; Bristol-Myers Squibb: Honoraria. Asano:Jannsen: Honoraria; Chugai: Honoraria. Kinoshita:Ono: Research Funding; Gilead: Research Funding; Zenyaku: Honoraria, Research Funding; Takeda: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Solasia: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria. Suzumiya:Chugai: Honoraria, Research Funding; Astellas: Research Funding; Eisai: Honoraria, Research Funding; Takeda: Honoraria; Toyama Chemical: Research Funding; Kyowa Hakko kirin: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria.


2020 ◽  
Author(s):  
Yuanyuan Lei ◽  
Wenting Huang ◽  
Qiuxiao Yu ◽  
Sha Feng ◽  
Guihua Shen ◽  
...  

Abstract Objective: To investigate the invasive capability and other clinicopathological features of conventional papillary thyroid carcinoma (CVPTC) with intralobular lymphatic dissemination.Methods: Seventy-three CVPTC patients receiving total thyroidectomy were analyzed in this study. The expression of BRAF-V600E, D2-40 and CD31 in all thyroid samples was detected by immunohistochemical staining (IHC). The results were evaluated by two pathologists and were statistically analyzed. In addition, the rate of positive BRAF-V600E expression and the clinical invasiveness of CVPTC with intralobular dissemination (ID-CVPTC), multiple primary CVPTC (MP-CVPTC) and single focus CVPTC (SF-CVPTC) were evaluated. The correlation between BRAF-V600E expression, lymphatic vessel density (LVD), microvessel density (MVD) and the clinicopathological characteristics of CVPTC were assessed.Results: Twenty-five ID-CVPTC, 17 MP-CVPTC and 31 SF-CVPTC cases were included in this study. The positive expression rate of BRAF-V600E in ID-CVPTC (92.0%) was significantly higher than that in MP-CVPTC (70.6%) and SF-CVPTC (71.0%), while no significant difference in expression between MP-CVPTC and SF-CVPTC was detected (P > 0.05). The expression of BRAF-V600E was not related to clinicopathological features, including age, gender, lymph node metastasis (LNM), bilateral involvement, presence of vascular tumor thrombus, capsule invasion, nerve invasion or the maximum tumor diameter (P > 0.05). The LVD in the ID-CVPTC group (9.74 ± 2.98) was higher than that in the non-ID-CVPTC group (7.46 ± 2.5) (P < 0.05). Compared with cases without adenolobar dissemination, ID-CVPTC was associated with a younger age, higher LNM rate, and increased capsule and vessel invasiveness (P < 0.05).Conclusions: ID-CVPTC shows more aggressive features, and intralobular lymphatic dissemination may be a potential biological indicator of poor prognosis.


2005 ◽  
Vol 15 (3) ◽  
pp. 432-437
Author(s):  
S. Pather ◽  
M. A. Quinn

The records of all patients with clear-cell ovarian cancer (CCC) who underwent complete surgical staging and chemotherapy between 1984 and 2001 were reviewed and 39 patients identified as suitable for study. The mean patient age was 56 years, and the stage distribution was as follows: stage I, 53%; stage II, 13%; stage III, 32%; and stage IV, 2%. One in three patients with stage I disease developed recurrent disease despite adjuvant chemotherapy. Seventy percent of tumors demonstrated a response to combination carboplatin and paclitaxel. Tumors which had either a partial response or failed to respond to first-line chemotherapy demonstrated no response to second-line nonplatinum chemotherapy. Endometriosis was identified in 31% of tumors, and 18% of patients developed deep venous thrombosis (DVT); however, neither endometriosis nor DVT was associated with a poorer outcome. CCC has a high recurrence rate in early-stage disease despite adjuvant treatment with cytotoxic chemotherapy. Advanced disease does respond to carboplatin and paclitaxel, which should be the chemotherapeutic regimen of choice. New second-line agents are urgently required.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 126-126
Author(s):  
Faisal A Siddiqui ◽  
James P. Dolan ◽  
John G. Hunter ◽  
Miriam A. Douthit ◽  
Lisa M. Bloker ◽  
...  

126 Background: Neoadjuvant chemoradiotherapy (NAT) followed by esophagectomy has been established as standard of care for early stage (II – III), resectable esophageal cancer (EC). Patients (pts) treated with NAT are more likely to be downstaged and have a complete (R0) resection. Additionally, pts with aggressive disease are more likely to progress during NAT and, consequently, avoid unnecessary surgery. The aim of the current report was to analyze the outcomes of trimodality therapy at the Knight Cancer Institute. Methods: A retrospective study of 124 pts who underwent NAT followed by esophagectomy for EC from 1999-2010 at our institution was performed. All pts were initially staged by imaging (EUS, CT and/or PET imaging) prior to commencing treatment. After esophagectomy, pathological staging was compared to initial staging to determine the effect of NAT. Results: There were 25 women and 99 men. Initial staging is shown in the table below. Patients received cisplatin, oxaliplatin or carboplatin with 5-FU plus concurrent radiotherapy (RT). RT total dose of 45 Gy to the tumor and regional nodes was given in 1.8 Gy daily fractions, followed by a boost to the tumor for final dose 50.4-54 Gy. 27 (21.8%) of the pts had a pathologic complete response. Additionally, 54 (43.6%) pts were downstaged by chemoradiation. Of the pts that had complete remission or were downstaged, pre-treatment clinical stage was Stage II (22 pts), Stage III (55 pts), and Stage IVa (4 pts). Conclusions: NAT was effective in complete remission or downstaging of two-thirds (81) pts, including 4 pts that were initially unresectable (Stage IVa) and successfully underwent subsequent esophagectomy. As has been shown previously, NAT is effective for downstaging prior to esophagectomy making it more likely that pts will undergo R0 resection. This study also demonstrated that some pts with clinically unresectable tumors could undergo successful esophagectomy after NAT. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9527-9527
Author(s):  
Georgia Sofia Karachaliou ◽  
Sarah Bass Carroll ◽  
Nirali M. Patel ◽  
Xiaobei Zhao ◽  
Guillaume Joe Pegna ◽  
...  

9527 Background: Activation of the WNT/β-catenin pathway is associated with low/absent tumor-infiltrating lymphocytes (TILs) and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. We aimed to investigate if APC/CTNNB1 mutations in melanoma pts are associated with TIL status, prediction of response to immunotherapy (IT), and overall survival (OS). Methods: Pts with CM and APC or CTNNB1 mutations identified in melanoma tumors using the TruSight Tumor 26 Illumina assay were enrolled. Demographics, clinical (stage, treatment response, follow-up), pathologic (TIL status), and molecular (BRAF/NRAS, C→T (i.e. UV signature) nucleotide transition, functional significance by IMPACT, mutant allele frequency (MAF) corrected from the % tumor) characteristics were investigated. Results: We identified a total of 25 pts (13 males; age at original diagnosis (median 61 yrs, range 22-78 yrs). CTNNB1 and APC mutations were mutually exclusive. 48% (12/25) had APC mutations and 52% (13/25) had CTNNB1 mutations; of which (i.e. CTNNB1 mutations) 69% (9/13) had absent TILs. 88% (22/25) of APC/CTNNB1 mutations had moderate functional significance, 64% (16/25) of the mutations had a C→T nucleotide change, 36% (9/25) had BRAFV600, and 20% (5/25) NRASQ61 mutations. 64% (14/22) of pts with stage II-III progressed to stage IV; of these 14 pts, 8 (57%) developed parenchymal BrM. 13 of the stage II-III 22 pts who progressed to stage IV received IT; of these 13 pts, 7 (53%) had absent TILs. APC/CTNNB1 mutations did not influence response to IT, irrespective of the MAF of the mutations. Of the 12 pts with MCM and measurable disease who received IT 9/12 had absent TILs and 7/12 responded. The median OS from the time of diagnosis of distant MCM (N = 17; 14 pts who progressed from initial stage II-III and 3 pts who were originally diagnosed with stage IV) was 18.8 months (range, 2.4-48.0 months). Conclusions: APC & CTNNB1 mutations are mutually exclusive. CTNNB1 mutations are more frequently associated with absent TILs. Pts with MCM had relatively shorter OS (18.8 months) in part due to development of BrM. In this small cohort APC/CTNNB1 mutations did not seem to impair response to immunotherapy.


Author(s):  
Dr. Amol R. R. Rajhans, MD ◽  
Dr. Deepak S. Howale

Breast cancer is the most common invasive cancer in women, and the second main cause of cancer death in women, after lung cancer. Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin. In 2017, around 252, 710 new diagnoses of breast cancer are expected in women, and around 40,610 women are likely to die from the disease. Awareness of the symptoms and the need for screening are important ways of reducing the risk. Material and Methods: This retrospective study was carried out in the department of Pathology, DCP Consultant Pathologist Shashwat Hospitals, Pune, a total of 38 retrospective breast carcinoma tissues were obtained from female patients. Representative paraffin blocks and haematoxylin and eosin (HandE)-stained sections were retrieved from the pathology department. The patients' records were reviewed to look for the patient age and the clinical stage of the disease. The stage of the cancer was reported according to the American Joint Committee of Cancer. As tissue and patient data was collected in an anonymous way no written or informed consent was required for the study purpose. Results and Observations: According to data by clinical staging Stage I, Stage II, Stage III and Stage IV were 16 (42.11%), 11(28.95%), 7 (18.42%) and 4 (10.53%) respectively. According to histology Stage I, Stage II, Stage III and Stage IV were 2 (5.26%), 11(28.95%), 24 (63.16%) and 1 (2.63%) respectively. Hand E-stained sections showed that tumour-infiltrating lymphocytes (TILs) were present in 31 of the 38 carcinomas (81.58%). Majority of theTILs were T lymphocytes and was present in all 31 cases. CD4+ cells were seen31 patients and CD 8+ were seen in 25 cases. B cells were seen in 21 cases. TILs were analysed according to the clinical stage of breast cancer, stages III and IV tumors showed significantly higher densities of total lymphocytes, T lymphocytes, and CD4+ lymphocytes as compared to stage II tumors. Lymphocyte immuno phenotypes and the total TILs also showed a high significantly positive correlation between each lymphocyte population/subpopulation and the total TILs. Conclusion: T and B lymphocytes were expressed in breast carcinoma with High prevalence of T lymphocytes CD4+ cells. However larger no of cases are required to confirm the findings and extensive large studies are required.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22182-e22182
Author(s):  
A. Munoz Llarena ◽  
A. Garcia ◽  
B. Suarez ◽  
M. Jangi ◽  
P. Garrido ◽  
...  

e22182 Background: Current microarray technologies allow the analysis of thousands of genes simultaneously. We analyze the gene expression profile of different samples from human colorectal carcinoma in relation with the clinical stage at diagnosis. Methods: Thirty-one patients were included: 13 with stage II (transmural invasion of the colonic wall without lymph node invasion), 10 with stage III (regional lymph node invasion) and 8 with stage IV at diagnosis (metastatic). RNA was extracted from fresh tumour samples, and the quantity and quality were assessed by spectrophotometric method and capilar electrophoresis. Tumoral samples were hibrizided with a pool containing non-tumoral colonic mucosa from 33 patients with colorectal cancer. Normalized crude data were used for the initial selection of the genes, using several univariate metrics (Matusita, Kullback-Leibler, Bhattachryya). A high confidence Bayesian network was used to compare the best ranked genes with the stage of the tumour at diagnosis. Results: We identified a group of 20 genes with potential prognostic value. Of them, nine genes (HAS1, LO9861, NHLRC2, ATP6V0E2, GTFH2H2, FLJ34077 , CASP12 and RP5–1077B9.4) were able to discriminate cases with stage II-III and those with stage IV, and 11 genes (MEA1, SPRY4, TLR8, SAMSN1, DGCR14, MRCL3, SMAD2, SFRS12, LAPTM4A, CD18 and FAM111A) could discriminate between patients with stage II or III, in 95% of the cases. Data were validated with 18 new patients with colorectal cancer using a quantitative method (RT- PCR). Conclusions: Only few genes are able to discriminate the clinical stage of the tumour at diagnosis with a fresh sample of the primary. Patients with an unfavourable signature might benefit of a more extensive initial work-up. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 253-253
Author(s):  
Rosemary Habib ◽  
Val Gebski ◽  
Kenneth Micklethwaite ◽  
Duncan McLeod ◽  
James Toh ◽  
...  

253 Background: In early and advanced colorectal cancer (CRC), there is limited data comparing the influence of mucinous (MAC) with non-mucinous adenocarcinoma (NMAC) histology on clinical outcomes. We investigated the association between histological type and outcomes in CRC. Methods: Medical records of patients with stage II, III and IV CRC referred to a tertiary centre in Western Sydney between 2009-2016 were examined and demographic and clinical information extracted. Key prognostic factors were modeled using log rank tests and proportional hazards (PH) regression methods in multivariate analyses. Results: Data on 686 patients was extracted. Median age was 70 years (19 – 94). Median follow up was 38.4 months. 98 patients (12%) had MAC and no differences in stage were observed at presentation between MAC and NMAC (p = 0.16). MAC was associated with increased prevalence of microsatellite instability (36% v 11% p < 0.01), high grade tumours (51% v 18% p < 0.01), female gender (61% v 45% p < 0.01) and right sided primary (65% v 40% p < 0.01). In stage II/III, MAC had comparable relapse free survival (RFS) versus NMAC (median 79 vs 97 months; P = 0.21). However, in the adjuvant chemotherapy group, a poorer RFS was seen for MAC (52 Vs 82 months, HR = 0.52, P = 0.03). In all patients with relapsed disease, MAC was more likely to be associated with peritoneal carcinomatosis (51% vs 26%; P < 0.01), and less likely to be associated with liver metastases (45% Vs 70%, P < 0.01) than NMAC. PH analysis of the MAC cohort revealed poorer RFS for LVI (HR 2.85; p = 0.03), T4 stage (HR 3.15, p = 0.01) and adjuvant chemotherapy (HR 5.49, p < 0.01). On multivariate analysis, T4 remained significant for poorer RFS. No differences were seen in OS in early stage CRC between MAC and NMAC. However, right sided and female gender with stage IV MAC had poorer OS (Right colon: HR 6.6; P = 0.03) (Female: HR 4.90, P = 0.03). Conclusions: MAC is associated with poorer RFS in early stage CRC irrespective of sidedness, and with poorer OS in right sided CRC. Given their poor response to adjuvant chemotherapy, novel adjuvant treatments should be considered for early MAC CRC. In the palliative setting, novel therapies and clinical trials are required for patients with MAC, particularly with right sided primaries.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jianhong Wu ◽  
Guangxin Li ◽  
Zeyou Wang ◽  
Yongliang Yao ◽  
Rui Chen ◽  
...  

MicroRNA-21 was upexpressed in gastric cancer (GC) indicating that it is a potential diagnostic biomarker for GC. In this study, 50 GC patients and 50 healthy controls were recruited. miR-21 levels in serum and peripheral blood mononuclear cells (PBMCs) were quantified using quantitative real-time PCR. CA199, and CEA were measured using electrochemiluminescence assay. The sensitivity and specificity of circulating miR-21, CA199 and CEA in GC diagnosis, the correlation of circulating miR-21 to clinicopathological features, and the diagnostic value of miR-21 in different GC stages were determined. The levels of miR-21 in both serum and PBMCs increased significantly in GC patients comparing to healthy controls; however, no correlation was observed between circulating miR-21 level and clinicopathological features. The sensitivity and specificity of miR-21 in serum and PBMCs, and CA199 and CEA in GC diagnosis were 88.4%, 79.6%, 81.3%, 73.4%, 60.5%, 55.9%, and 68.6%, 59.3%, respectively. The positive prediction rates of circulating miR-21 in GC stages I to IV were all around 90%, while those of CA199 and CEA were around or less than 50%. Our data suggest circulating miR-21 (both in serum and in PBMCs) can serve as a good biomarker for GC and could be used in diagnosis of early (stage I) and late GC (stage IV).


1983 ◽  
Vol 69 (2) ◽  
pp. 123-127
Author(s):  
Vittorio Pengo ◽  
Giuseppe Cartei ◽  
Dario Casara ◽  
Otello Daniele ◽  
Mario V. Fiorentino

Forty-four patients (9 stage II, 15 sage III, 7 stage IV, and 13 in complete remission) with Hodgkin's disease without any clinical coagulation disorder were studied. Fibrinogen behavior was evaluated by measuring fibrinogen level and using 1251-fibrinogen, the half-life, survival and fibrinogen turnover. Platelet count and fibrinogen/fibrin degradation products (FDP) were also assayed. The fibrinogen half-life, survival and turnover were significantly longer and faster, than those found in 10 healthy subjects, in stage II, III and IV subjects (p < 0.001, p < 0.001, p < 0.05 for stage II; p < 0.001, p < 0.001, p < 0.001 for stage III; p < 0.005, p < 0.005, p < 0.001 for stage IV, respectively). In most cases, FDP values were within the normal range, although they were significantly higher than those of control group in stages III and IV. Intravascular coagulation and fibrinolysis were not found in the 13 patients with complete remission. In these patients, the behavior of fibrinogen was normal, suggesting that the parameters studied are related to the presence of the tumor, and can be useful in monitoring the state of remission.


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