The Philadelphia chromosome was the first genetic abnormality discovered in cancer (in 1960), and it was found to be consistently associated with CML. The description of the Philadelphia chromosome ushered in a new era in the field of cancer cytogenetics. Accumulating genetic data have been shown to be intimately associated with the diagnosis and prognosis of neoplasms; thus, karyotyping is now considered a mandatory investigation for all newly diagnosed leukemias. The development of FISH in the 1980s overcame many of the drawbacks of assessing the genetic alterations in cancer cells by karyotyping. Karyotyping of cancer cells remains the gold standard since it provides a global analysis of the abnormalities in the entire genome of a single cell. However, subsequent methodological advances in molecular cytogenetics based on the principle of FISH that were initiated in the early 1990s have greatly enhanced the efficiency and accuracy of karyotype analysis by marrying conventional cytogenetics with molecular technologies. In this review, the development, current utilization, and technical pitfalls of both the conventional and molecular cytogenetics approaches used for cancer diagnosis over the past five decades will be discussed.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia/diagnosis/genetics/pathology ; Neoplasms/*diagnosis/genetics/pathology ; Prognosis

Tumor heterogeneity is one of the characteristics of malignant tumors, which can cause differences in tumor growth rate, invasion, migration, drug sensitivity and prognosis. Discoveries and development upon on tumor-driver genes and targeted therapy paved the way on dealing with cancer diagnosis and treatment. However, the existence of tumor heterogeneity makes malignant tumor more hardly to overcome. It is generally present and far more complicated during the process of cancer recurrence, development and evolution. Thus, it has becoming key areas in precision medicine regarding to designing optimal therapeutic approaches targeting the mechanisms and phenotypes of tumor heterogeneity, based on novel detecting techniques and new concepts and theory. This review summarized the current references on tumor heterogeneity, in order to better understand the function and mechanisms, and eventually manage tumor heterogeneity through various methods.
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Evolution, Molecular ; Humans ; Mutation ; Neoplasms ; diagnosis ; genetics ; pathology ; therapy

OBJECTIVEThe purpose of this study was to investigate the relationship between the results of flowcytometry analyses of different clinical stage, location, pathologic grade and cell origin of oral and maxillofacial non-Hodgkin's lymphoma (NHL), and the diagnostic value of flowcytometry analysis in lymphoma.

METHODThis study analyzed 50 oral and maxillofacial NHL cases and 10 reactive lymph nodes (formalin fixed and paraffin embedded) by flowcytometry (FCM).

RESULTSReactive lymph nodes were all diploid. The diploid rate of NHL was 54%, and aneuploidy rate was 46%. There was statistically significant difference between reactive lymph nodes and NHL in the DNA ploidy status and cell cycle data (SPF, CV, S + G2/M, DI). The S phase fraction (SPF) and S + G2/M had close relationship with the grade of NHL. SPF value and DNA ploidy status had no obvious relationship with the prognosis.

CONCLUSIONThe results suggested that the FCM had diagnostic value in NHL, especially when the morphological diagnosis was difficult. Although the cell cycle data had no prognostic value, SPF and SPF + G2/M can show the proliferative status of NHL, which can help clinical doctor select therapeutic method.

Cell Cycle ; DNA, Neoplasm ; analysis ; Facial Neoplasms ; diagnosis ; genetics ; pathology ; Flow Cytometry ; Humans ; Lymphoma, Non-Hodgkin ; diagnosis ; genetics ; pathology ; Maxillary Neoplasms ; diagnosis ; genetics ; pathology ; Mouth Neoplasms ; diagnosis ; genetics ; pathology ; Ploidies ; Prognosis

OBJECTIVETo investigate the value of fluorescence in situ hybridization (FISH) detection of human telomerase RNA component (hTERC) gene amplification in screening of cervical lesions.

METHODSA total of 146 post-thinPrep cytology test (TCT) samples were analyzed using FISH by two-color interphase probe targeting hTERC gene at chromosome 3q26 and the data were compared with the cytological and histological results.

RESULTSFISH analysis was successful in 120 cases (20 cases of normal and 100 abnormal cases by TCT). Gene amplification of hTERC by FISH had a positive correlation with the cytological (r = 0.465, P < 0.01) and histological grade results (r = 0.610, P < 0.01). Extra copies of hTERC were seen in 28.6% (6/21) of CINI, 61.1% (11/18) of CINII, 75.0% (18/24) of CINIII and 91.7%(22/24) of squamous cell carcinoma, respectively. None (0/13) of the inflammation cases showed hTERC amplification. The sensitivity and specificity for detecting high grade lesions by FISH were 77.3% (51/66) and 82.4% (28/34); and the positive and negative predictive values were 89.5% and 65.1%, respectively. The rate of hTERC gene gain in high grade lesions was significantly higher than that in the low grade lesions (χ(2) = 32.550, P < 0.01). Combined with the high copy numbers, the sensitivity for detecting high grade lesions was increased to 81.2%.

CONCLUSIONSDetection of hTERC gene amplification by FISH improves the screening efficiency of high-risk cervical epithelial lesions. The presence of high copy numbers of hTERC correlates with the presence of high grade cervical dysplasia.

Adult ; Aged ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; genetics ; pathology ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; RNA ; genetics ; Telomerase ; genetics ; Uterine Cervical Neoplasms ; diagnosis ; genetics ; pathology ; Uterine Cervicitis ; diagnosis ; genetics ; pathology ; Young Adult

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.
Humans ; Urinary Bladder Neoplasms/genetics* ; Carcinoma, Transitional Cell/pathology* ; Urinary Bladder/pathology* ; Diagnosis, Differential ; Retrospective Studies ; Mutation ; Cystitis/genetics* ; Neoplasms, Glandular and Epithelial/diagnosis* ; Papilloma/diagnosis* ; Telomerase/genetics*

Adenocarcinoma, Follicular ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Kidney Diseases, Cystic ; genetics ; metabolism ; pathology ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; Translocation, Genetic

Adolescent ; Adult ; Biomarkers, Tumor ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; genetics ; pathology ; Octamer Transcription Factor-3 ; genetics ; Ovarian Neoplasms ; diagnosis ; genetics ; pathology ; Testicular Neoplasms ; diagnosis ; genetics ; pathology

Biopsy, Fine-Needle ; methods ; Breast ; metabolism ; pathology ; Breast Neoplasms ; diagnosis ; genetics ; pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lymph Nodes ; metabolism ; pathology ; Lymphoma ; diagnosis ; genetics ; pathology ; Pancreas ; metabolism ; pathology ; Pancreatic Neoplasms ; diagnosis ; genetics ; pathology

Carcinoma, Renal Cell ; classification ; diagnosis ; genetics ; pathology ; Chromosomes, Human ; Humans ; Immunohistochemistry ; methods ; Kidney Neoplasms ; classification ; diagnosis ; genetics ; pathology ; Translocation, Genetic

Biomarkers, Tumor ; Breast Neoplasms ; classification ; diagnosis ; genetics ; pathology ; Carcinoma, Basal Cell ; classification ; diagnosis ; genetics ; pathology ; Genes, BRCA1 ; Humans ; Mutation