K-RAS, B-RAF and GNAS Gene Status and Immunohistochemistry Analysis of Mucinous Neoplasm of Appendix

2020 ◽  
Author(s):  
xinyu ren ◽  
Yin Cheng ◽  
Tao Lu ◽  
Junliang Lu ◽  
Yan Wu ◽  
...  

Abstract AIM Low grade appendiceal mucinous neoplasm (LAMN) and serrated lesions are sometimes hard to differentiate from morphology. We try to characterize them from the immunohistochemical and molecular perspective and to reflect the difference between them. METHODS 25 appendix neoplasm including 13 LAMNs, 12 serrated lesions were selected from January 2013 to December 2014. Immunohistochemical analyses for cytokeratin 20, MUC6, MUC5AC, MUC1, Ki-67, P53 and mismatch repair (MMR) proteins including MLH1, PMS-2, MSH-6, MSH-2 were performed. Microsatellite instability (MSI) status was also evaluated. Besides, we detect K-RAS, B-RAF and GNAS gene mutation status of these lesions. RESULTS Immunochemically, 83.3% serrated lesions showed scattered CK20 staining in the deep crypt, which was less so for LAMNs. As for mucin expression, MUC5AC had slightly higher positive rate in LAMNs and than in serrated lesions.MUC1 was significantly higher expressed in LAMNs than in serrated lesions. 46.1% LAMNs have P53 expression in deep crypt, while P53 was negative in the deep crypt of serrated lesions. 58.3% serrated lesions had deficient MMR protein expresion pattern compared to 23.1% of LAMNs. B-RAF mutation was detected in 3 cases, all were serrated lesions. K-ras and GNAS mutation was detected in both LAMNs and serrated lesions. CONCLUSION Immunohistochemical panel comprising markers such as CK20, MUC5AC, MUC1, Ki-67 and P53, with genotyping covering hotspots of the KRAS, BRAF and GNAS genes can help the differential diagnosis of low grade appendix neoplasm.

Author(s):  
Basumitra Das ◽  
Kurimella Vamsya Raj ◽  
Bhagyalakshmi Atla

Background: Astrocytomas form the largest group of gliomas (>75%) and diffusely infiltrating    accounting for more than 60% of all the primary brain tumors. The ki67 proliferative index is a potent biologic marker that estimates the growth of neoplasms quantitatively and thus will aid in identifying the prognosis for patients with neoplasms.  The aim of the research work was to study various histopathological and clinical features of Astrocytomas in detail, to evaluate Ki-67 proliferative index in patients of Astrocytomas and to compare the results of Immunohistochemistry with histological grade of Astrocytomas.Methods: A   total   number   of    40 cases of   Astrocytomas were included in the study.  Ki-67 immunostaining was done on all cases and compared with WHO histological grading of astrocytomas.Results: The mean Ki‑67 LI in Grade I astrocytomas was 4.66, range 4-5 ,  in Grade II astrocytomas mean was 8.07, range 5-12 ,in Grade III astrocytomas mean was 13.5 , range 8-20,  in Grade IV astrocytomas mean was 22.93, range 15-50. There was a highly significant correlation between the histopathological grade of astrocytomas and Ki-67 LI (p<0.05).Conclusions: The monoclonal antibody Ki-67 has proven its prognostic and diagnostic power in astrocytic tumors. Ki-67 LI is the simplest and the most reliable method for evaluating cell proliferation. Ki-67 LI increased with histological grade and the difference between low grade (I and II astrocytomas) and high grade (grade III and IV) is significant. In the present study Ki-67 LI is not dependent on factors like age and sex and is solely dependent on histological grade.


2010 ◽  
Vol 25 (3) ◽  
pp. 150-156 ◽  
Author(s):  
Emilio Fiore ◽  
Daniela Campani ◽  
Ilaria Muller ◽  
Valentina Belardi ◽  
Elisa Giustarini ◽  
...  

Purpose Insulin-like growth factor-II (IGF-II) is an important regulator of tumor growth in breast cancer. In this study we have examined the prognostic value of IGF-II mRNA expression in breast cancer and its relationship to other predictive parameters. Patients Sixty-eight women with infiltrating ductal carcinoma were given the same treatments including mastectomy and antitumoral therapies and followed up for 5 years. Results The overall 5-year survival rate was 73.5% (55/68). IGF-II mRNA was expressed in 33/64 patients (51.6%) and had no significant impact on survival. The expression of estrogen receptor (ER) and progesterone receptor (PgR) did not significantly affect the 5-year survival, but in the presence of an IGF-II mRNA signal, the survival of ER- and PgR-negative patients (n=9) was lower than that of ER- and PgR-positive patients (n=15), although the difference was not significant. The 5-year survival was not significantly different between Ki-67-positive and negative patients, but in the IGF-II positive group Ki-67-positive patients (n=7) had a significantly poorer prognosis than Ki-67-negative patients (n=26). The expression of p53 protein was associated with a poorer prognosis: 6/11 (54.5%) p53-positive patients died in the first 26 months of follow-up and 5 of these 6 patients (83.3%) also had positive IGF-II mRNA expression. Conclusions IGF-II mRNA expression per se is not an independent predictive factor in breast cancer but may be a marker of poor prognosis when associated with other prognostic factors such as Ki-67 index and p53 expression.


2021 ◽  
pp. 1-8
Author(s):  
Tatsuro Yamaguchi ◽  
Kohei Murata ◽  
Tetsuya Shiota ◽  
Hiroshi Takeyama ◽  
Shingo Noura ◽  
...  

Introduction: Recently, “low-grade appendiceal mucinous neoplasms” (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN. Methods: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017. Results: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10). Conclusions: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.


2021 ◽  
pp. 62-69
Author(s):  
Tsubasa Yoshida ◽  
Yohei Kojima ◽  
Ryusuke Shimada ◽  
Hidesato Tanabe ◽  
Koichi Tabei ◽  
...  

Duodenal tumors with a sporadic adenoma-carcinoma sequence are extremely rare. For such clinically suspected cases without a specific family history, performing a comprehensive gene search is important to understand the germline mutation background. We present a 68-year-old woman without a genetic or familial history of familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, or Lynch syndrome who presented to Kosei Hospital, Japan, with exertional dyspnea induced by abdominal pain lasting 3 weeks. A duodenal tumor was suspected by contrast-enhanced computed tomography. Esophagogastroduodenoscopy showed a lesion accompanied by a white microprotuberance on the descending part of the duodenum opposite the papilla, with a giant ulcerative lesion at the center of the white lesion. Biopsy revealed a low-grade adenoma, high-grade adenoma, and adenocarcinoma. Immunohistochemical analysis of the adenoma and adenocarcinoma showed Ki-67, p53, cytokeratin 20, caudal-type homeobox 2, and carcinoembryonic antigen positivity and cytokeratin 7 negativity. The findings suggested the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma. However, in the mutational analysis using next-generation sequencing, c.4348C&#x3e;T (p.Arg1450Ter) mutation in APC was detected in all normal mucosal, adenoma, and carcinoma tissues. This mutation is common in FAP patients. Even if the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma is suggested in cases without a familial FAP history, as in this case, genetic analysis may reveal FAP. Thus, performing a comprehensive genetic analysis of duodenal carcinoma patients with a possible adenoma-carcinoma sequence is necessary to explore their genetic background.


2007 ◽  
Vol 64 (11) ◽  
pp. 753-758
Author(s):  
Vesna Zivkovic ◽  
Aleksandar Petrovic ◽  
Biljana Djordjevic ◽  
Vuka Katic ◽  
Jasmina Gligorijevic ◽  
...  

Background/Aim. The aim of this study was to apply computer- assisted methodology in assessment of Ki-67 positivity in "adenoma-like" dysplasia associated lesions or masses (DALMs), and carcinoma in ulcerative colitis (UC), and to determine a new approach to grading of Ki-67 staining intensity. Methods. Immunohistochemical slides were quantitatively analyzed for estimation of proportion and intensity of Ki-67 positive-stained cells in a total of 50 "adenoma-like" DALMs (27 with low-grade dysplasia and 23 with high-grade dysplasia), and 17 adenocarcinomas associated with UC. The four grades of immunohistochemical staining intensity were established by an automated classification of nuclear optical densities. Results. The Ki-67 labeling index (LI) in low-grade dysplasia was significantly lower than in high-grade dysplasia, and carcinoma (p < 0.001). The Ki-67 LI of carcinomas was not significantly different from the value obtained in highgrade dysplasia (p > 0.05), however having the difference in percentage values of the moderate stained nuclei (p < 0.05). The overall average values of chromogene nuclear optical density, showed statistically significant differences between DALMs and carcinoma (p < 0.05), although not between normal mucosa and low-grade dysplasia (p > 0.05). Conclusion. The obtained results imply, according to the overall percentage of labeled nuclei, that high-grade dysplasia is very close to carcinoma, while there is the difference in the percentage of moderately stained nuclei. We showed that Ki-67 positivity have a different internal distribution which could be useful in analysing these lesions. These findings also, indicate the important biological differences between low-grade dysplasia and carcinoma in UC, and a low proliferative potential of the former. Automated image analysis permits an objective estimation of Ki-67 immunohistochemical staining in UCassociated dysplasia and carcinoma.


2020 ◽  
Vol 24 (2) ◽  
pp. 145-155 ◽  
Author(s):  
G. Y. Kudryavtsev ◽  
L. V. Kudryavtseva ◽  
L. M. Mikhaleva ◽  
Y. Y. Kudryavtseva ◽  
N. A. Solovyeva ◽  
...  

Prostate cancer (PC) remains an urgent public health problem, especially in developed countries. The use of immunohistochemical research methods in addition to the morphological classification of prostate adenocarcinomas allows a more accurate diagnosis and prognosis of the disease. The aim of the study is to identify isoforms of P53 using clones of mouse antibodies (D-07 and Y5; Epitomics, USA) in prostate cancer with different proliferative activity and the degree of malignancy. Materials and Methods: The work included surgical material for prostate resection and prostatectomy, as well as biopsy specimens (56 cases in total). An immunohistochemical study was carried out with the Ki-67 marker, as well as with mouse monoclonal antibodies (D-07 and Y5) to the P53 protein, interacting with its wild and mutant isoforms. The significance of the difference in the samples was determined using the Mann-Whitney U-test, correlation relationships were determined using the Spearman coefficient. Results: Expression of P53 upon interaction with antibodies D-07 and Y5 was determined in 56.3% and 39.6%, respectively. A statistically significant direct correlation was found between the severity of P53 expression when interacting with Y5 antibodies and the degree of tumor differentiation (rs = 0.567, p 0.05), as well as between the expression level of this protein and tumor proliferative activity (rs = 0.698, p 0.05). Conclusion: Antibodies of clone D-07, interacting with both wild and mutant isoforms of P53 protein, show positive expression in adenocarcinomas of all degrees. Expression of the mutant P53 protein is most pronounced in low-differentiated carcinomas and correlates with high proliferative activity of tumor cells, which may be associated with a loss in the induction of P53-dependent apoptosis.


2021 ◽  
Vol 4 (1) ◽  
pp. 16-23
Author(s):  
Adrian Dumitru ◽  
Ana Ciongariu ◽  
Cătălin Aliuş ◽  
Dan Dumitrescu ◽  
Sergiu Andrei Iordache ◽  
...  

Abstract Bednar tumor is a rare cutaneous neoplasm, regarded as a variant of dermatofibrosarcoma protuberans with melanotic colonization and it usually affects young and middle-aged adults or children. This lesion is considered a low-grade malignant tumor, which can be associated with multiple local recurrences after surgical excision. Although a rare phenomenon, these lesions may undergo fibrosarcomatous transformation, which implies a poorer prognosis of the disease, as the tumor has a more locally aggressive behavior and patients might also develop distant metastases. We present the case of a 53-year-old female patient, with no significant medical history, who presented with a subcutaneous nodule on her upper back, for which a wide surgical excision was performed. The gross examination of the specimen showed a solitary protuberant grey-white nodule with a bluish shade and flecked with pigment. The microscopic examination revealed a malignant proliferation with a predominantly fascicular growth pattern, composed of spindle cells with highly pleomorphic nuclei and high mitotic rate, as well as the presence of dendritic cells with abundant melanin. Upon immunohistochemical analysis, the proliferation showed negative staining for CD 34 and AE 1/3, whereas the scattered dendritic cells stained positive with S100 protein. Ki 67 was positive in 15% of the tumor cells and the absence of p53 expression was noted. Thus, the diagnosis of Bednar tumor with fibrosarcomatous transformation was established. The aim of this paper was to gain further knowledge about the histopathological and immunohistochemical features, as well as about the treatment of Bednar tumor, especially considering its rarity.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yiyan Lu ◽  
Fang Li ◽  
Ruiqing Ma ◽  
Lan Fang ◽  
Changhai Qi

ObjectiveTo investigate the clinicopathological features and follow-up of low-grade appendiceal mucinous neoplasms (LAMNs) confined to the appendix.MethodsThe clinicopathological features, pathological primary tumor (pT) staging and follow-up of 22 patients with LAMNs confined to the appendix were analyzed retrospectively.ResultsOf 22 patients with LAMNs, 14 were pTis (eight pTism and six pTisf), six were pT3, and two were pT4a. The appendiceal diameter was significantly larger for pTisf than for pTism. The interval between first symptoms and surgery was longer for pTisf than for pTism, but not significantly different. No significant differences were found between the pT stages and appendiceal diameter or in the interval between the first symptoms and surgery. Pathomorphologically, the epithelial structures were mainly flat (100%), undulating or scalloped (82%); a few showed filiform villous hyperplasia (46%), and seven (32%) had serrated lesions in the background. Diverticula may be associated with LAMNs, and the location of acellular mucin caused by diverticula affected the pT stage of the LAMNs. The immunohistochemistry information showed the same pattern with cytokeratin 7 (CK7) negative, cytokeratin 20 (CK20) positive and caudal type homeobox 2 (CDX-2) positive. No lymph node metastasis was found. The lack of treatment guidelines for LAMNs confined to the appendix and different acceptances of patients of preventive intervention led to varied clinical treatments. However, we found no short-term benefits of prophylactic extended resection or hyperthermic intraperitoneal chemotherapy.ConclusionLAMNs confined to the appendix are rare and must be differentiated from serrated lesions and diverticula. LAMNs with different pT stages have inert biological behavior. Determining the long-term effects of preventive treatment on survival and recurrence requires more data and a longer follow-up.


2021 ◽  
Author(s):  
Yiyan Lu ◽  
Changhai Qi ◽  
Hongbin Xu ◽  
Mulan Jin

Abstract Purpose: To identify clinicopathological features for the differential diagnosis of appendiceal serrated lesions and polyps (SPs) and low-grade appendiceal mucinous neoplasm (LAMN) for the purpose of avoiding over‐diagnosis.Methods: Clinical data and pathological features of 66 patients with SPs diagnosed at the Aerospace Center Hospital between January 2013 and January 2021 were collected and compared to 22 cases of LAMN.Results: SPs, compared with LAMN, are likely to be associated with acute inflammation (SPs 53.0% vs. LAMN 18.2%), and may be located in the appendix partly, although with smaller diameter (average 9.6 vs. 27.2 mm); epithelial structures of serrated (100% vs. 22.7%) and filiform villous (47.0% vs. 18.2%) were often found in SPs. SPs occasionally show attenuated or flattened morphology (16.7% vs. 100%) and undulating or scalloped (7.6% vs. 40.9%) structures, and can also be accompanied by diverticulum (18.2% vs. 18.2%) and acellular mucin in the appendiceal wall (16.7% vs. 54.5%), which causes confusion with LAMN. The key point of the differential diagnosis is to observe whether the muscularis mucosa exists (loss, 0% vs. 100%) and fibrosis of the appendiceal wall (0% vs. 100%). SMA immunohistochemistry can assist in the diagnosis. Calcification is also indicative of LAMN.Conclusions: The epithelial structure of SPs can appear flattened and focally scalloped, and can be accompanied by mucin in the appendiceal wall, which may appear as complex lesions, easily over-diagnosed as LAMN. Key differential diagnostic features are identifying the structure of lamina propria, determining whether the muscularis mucosa exists, and whether the appendiceal wall is fibrotic.


Sign in / Sign up

Export Citation Format

Share Document