molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.

Collision tumor of primary malignant lymphoma and adenocarcinoma in the colon diagnosed by molecular pathology:A case report and literature review

BACKGROUND Collision tumors of primary malignant lymphoma and adenocarcinoma in the colon are rare.Primary diffuse large B-cell lymphoma(DLBCL)–adenocarcinoma collision tumors are especially rare.CASE SUMMARY A 74-year-old woman presented with abdominal pain of 1 mo duration.Biopsy under colonoscopy revealed adenocarcinoma of the ascending colon.Subsequently,the patient underwent laparoscopic radical resection of right colon cancer with lymph node dissection.A collision tumor was found incidentally through postoperative pathological sampling.Genetic analysis showed a collision tumor of DLBCL with germinal center B-cell subtype and TP53 mutation,and adenocarcinoma arising in a tubulovillous adenoma in the colon,with BRAF mutation and mutL homolog 1 promoter methylation.The patient died 3 mo after surgery.To our knowledge,this is the 23rd reported case of collision tumor of colorectal adenocarcinoma and lymphoma.The mean age of the 23 patients was 73 years.The most common site was the cecum.There were 15 cases with followup data including 11 living and four dead with a 3-year overall survival rate of 71.5%.CONCLUSION Based on pathological and genetic analysis,surgery combined with chemotherapy or chemoradiotherapy may have good therapeutic effects for collision tumor.

Relationship between magnetic resonance imaging and molecular pathology in patients with glioblastoma multiforme

Background Glioblastoma multiforme （GBM） is the most common and lethal primary brain tumor in adults. Magnetic resonance imaging （MRI） is routinely used in the diagnosis, characterization and clinical management of GBM. The diagnosis and treatment of GBM is largely guided by histopathology and immunohistochemistry. This study aimed to identify the relationship between magnetic resonance features and molecular pathology of GBM. Methods MRI images of 43 glioblastoma patients were collected. Four imaging features, degree of edema, contrast tumor enhanced/T2 ratio, multiple lesions and tumor across the midline, were selected to identify their relationship with P53, Ki-67 and O6-methylguanine-DNA methltransferase （MGMT） expression in patients with GBM. The relationship between imaging features and molecular pathology was studied by chi-square test using the software SPSS 13.0. Results High expression of P53 was found correlated with low contrast tumor enhancedFF2 ratio, low expression of Ki-67 was correlated with multiple lesions and high expression of KI-67 may be related with tumor across the midline, low expression of MGMT was correlated with edema. Conclusion Some MRI features such as the degree of edema, contrast tumor enhanced/T2 ratio, multiple lesions and tumor acrossing the midline are correlated with P53, Ki-67 and MGMT of GBM.

Molecular pathology and clinical implications of diffuse glioma

The prognosis for diffusely infiltrating gliomas at World Health Organization(WHO)grade 2-4 remains dismal due to their heterogeneity.The rapid development of genome-wide molecular-profiling-associated studies has greatly promoted the accuracy of glioma classification.Thus,the latest version of the WHO classification of the central nervous system tumors published in 2021 has incorporated more molecular biomarkers together with histological features for the diagnosis of gliomas.Advanced usage of molecular pathology in clinical diagnostic practice provides also new opportunities for the therapy of patients with glioma,including surgery,radiotherapy and chemotherapy,targeted therapy,immunotherapy,and more precision clinical trials.Herein,we highlight the updates in the classification of gliomas according to the latest WHO guidelines and summarize the clinically relevant molecular markers by focusing on their applications in clinical practice.We also review the advances in molecular features of gliomas,which can facilitate the development of glioma therapies,thereby discussing the challenges and future directions of molecular pathology toward precision medicine for patients with glioma.

Clinical management and survival outcomes of patients withdifferent molecular subtypes of diffuse gliomas in China(2011–2017):a multicenter retrospective study from CGGA

Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors.The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing,and 1p/19q codeletion was detected with fluorescence in situ hybridization.The median clinical follow-up time was 1,076 days.T-tests and chi-square tests were used to compare clinicopathological characteristics.Kaplan‒Meier and Cox regression methods were used to evaluate prognostic factors.Results:Our cohort included 15.5%lower-grade gliomas,IDH-mutant and 1p/19q-codeleted(LGG-IDHm-1p/19q);18.1%lowergrade gliomas,IDH-mutant(LGG-IDHm);13.1%lower-grade gliomas,IDH-wildtype(LGG-IDHwt);36.1%glioblastoma,IDHwildtype(GBM-IDHwt);and 17.2%glioblastoma,IDH-mutant(GBM-IDHm).Approximately 63.3%of the enrolled primary gliomas,and the median overall survival times for LGG-IDHm,LGG-IDHwt,GBM-IDHwt,and GBM-IDHm subtypes were 75.97,34.47,11.57,and 15.17 months,respectively.The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%.We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors.We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm,and in prolonging post-relapse survival for the 2 recurrent GBM subtypes.Conclusions:By controlling for molecular subtypes,we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.

Understanding the molecular pathogenesis and prognostics of bladder cancer： an overview

The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high- grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article oudines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.

The Analysis of High-Risk Molecular Markers for Cervical Cancer Patients under Thirty-Five

OBJECTIVE To explore molecular markers for cervical cancer in female patients below thirty-five years of age, so that the markers may be used to formulate a prognosis and to provide some useful targets for improving therapy. METHODS Pathological data were collected from 64 cervical cancer patients under the age of 35 from June, 1995 to June, 2000 in our institution. The data were retrospectively analyzed as a study group, and compared to data obtained from 90 cervical cancer cases over the age of 35 as controls who underwent treatment during the same time period. Immuno-histochemical and quantified image analyses were conducted to look for differences between the two groups in expression of survivin, p27, CD44v6, MMP-2 and TIMP-2. RESULTS The overall 5-year survival rate (65.6%) of the study group was significantly lower (P<0.05) compared to the control group (84.4%). The expression of survivin, MMP -2 and CD44v6 was much higher in the younger study group compared to the older control group, but TIMP-2 displayed higher expression in the control group (P<0.05). There was no significant difference in p27 expression between the two groups (P>0.05). CONCLUSION Young women patients with cervical cancer have a poorer prognosis compared to old women. Our study reveals that survivin, MMP-2, TIMP-2 and CD44v6 expression have a correlation with shorter 5-year survival. Improvement in the prognosis for young cervical cancer patients can be expected using biomedical therapy which targets these molecular markers.

Genomic and genetic alterations influence the progression of gastric cancer

Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.

In the Basis of Hashimoto’s Thyroiditis, to Form Papillary Thyroid Carcinoma, Metastasized and Then to De-Differentiate into Poorly Differentiated Squamous Cell Carcinoma

Thyroid squamous cell carcinoma is very rare. At present, it is limited to case reports. Since the thyroid follicular epithelium is the non-squamous epithelium, how primary squamous cell carcinoma (SCC) of the thyroid occurs is still a controversial issue. Hashimoto’s thyroiditis (HT) is considered to be an independent risk factor for thyroid cancer, under the basis of HT, how tumor cells evolve and develop to papillary thyroid carcinoma (PTC), and particularly to de-differentiate into SCC is elusive. We report a 72-year-old female patient who developed multiple subtypes of PTC on a basis of HT, and finally to de-differentiate into SCC within the local foci of lymph node metastasis. We found that there was a variety of sub-types of PTC in this patient in the background of HT. SCC was found within local lymph node metastasis. Pathomorphology, immunohistochemistry, and molecular pathology have confirmed that the SCC was derived from PTC, and then developed into poorly differentiated SCC and/or anaplastic carcinoma. We also conducted a comprehensive literature review.

Molecular profiling and patient selection for the multimodal approaches for patients with resectable colorectal liver metastases

Colorectal cancer represents the third most common cancer and about 20%are diagnosed with synchronous metastatic disease.From a historical point of view,surgery remains the mainstream treatment for resectable colorectal liver metastases(CRLM).Furthermore,disease outcomes are improving due significant advances in systemic treatments and diagnostic methods.However,the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question.Thus,patient selection combining image workouts,time of recurrence,positive lymph nodes,and molecular biomarkers can improve the decision-making process.Nevertheless,molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment.Tumor biomakers,genetic profiling,and circulating tumor DNA have been used to offer as much personalized treatment as possible,based on the precision oncology concept of tailored care rather than a guideline-based therapy.This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

Genetic characteristics and molecular diagnostics of bone tumors

The diagnosis of primary tumors of bone relies heavily on clinicopathological and radiological correlation and is often best performed in a multidisciplinary setting.Bone tumors comprise a heterogenous category of human lesions ranging from benign to malignant neoplasms.These tumors affect a wide age range and can become problematic for diagnosis when less common entities are encountered.Traditionally the pathological diagnosis of many bone tumors has been based primarily on the evaluation of hematoxylin and eosin-stained glass slides,sometimes combined with ancillary diagnostic techniques such as immunohistochemistry,conventional cytogenetics,fluorescence in situ hybridization,and polymerase chain reaction-based assays.More recently,the advent of massively parallel sequencing-based techniques has opened new avenues for diagnostic testing in bone tumors;however,these new testing modalities are sensitive to traditional decalcification procedures that are commonly used in the routine processing of bony specimens.Herein we provide a focused review concentrating on the molecular genetic features of bone tumors with specific,recurrent genetic alterations that make them appealing targets for directed ancillary testing by conventional or molecular techniques.In addition,specimen handling with regards to decalcification procedures are discussed and the different types of testing modalities available are reviewed.

Imaging biomarkers for predicting poor prognosis of hepatocellular carcinoma: a review

Hepatocellular carcinoma(HCC)is a primary malignancy of the liver with a high mortality rate.Heterogeneity is the main biological characteristic of HCC,which manifests through the different biological behaviors of each phenotype and ultimately,affects patient prognosis and treatment efficacy.Various aggressive biological behaviors are considered to be associated with the poor prognosis of HCC patients including poor differentiation,microvascular invasion,intracellular fat accumulation,invasive growth,bile duct invasion or tumor thrombosis,and tumor spread and metastasis,and have been reported as prognostic biomarkers.In addition,HCC results from multifactor synergistic damage,and various factors related to genetics,molecular pathology and immunohistochemistry such asβ-catenin,Ki67,cytokeratin-19,and epithelial cell adhesion molecule have an impact on HCC differentiation and prognosis.This article is an overview of the biological behaviors that lead to poor prognosis of HCC,and the roles of morphological and quantitative noninvasive imaging biomarkers in the evaluation and prediction of these behaviors.Some common biomarkers related to genetics,molecular pathology and immunohistochemistry are also briefly summarized.It is hoped that this review will provide clinicians and radiologists with an update on the development of liver imaging,and provide directions for the combination of radiology,genetics,molecular pathology and histopathology to better predict the prognosis of HCC patients.

Human microbiome and prostate cancer development:current insights into the prevention and treatment

The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease.The human microbiome may influence prostate cancer development.To date,several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk.Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men,demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment.In healthy individuals,the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism.Dysbiosis may contribute to the emergence of health problems,including malignancy through affecting systemic immune responses and creating systemic inflammation,and changing serum hormone levels.In this review,we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract,gastrointestinal tract,oral cavity,and skin might affect the risk of developing prostate cancer.Furthermore,we discuss strategies to target the microbiome for risk assessment,prevention,and treatment of prostate cancer.