Histologic Grade



Histologic Grade










Approximately 20% of invasive carcinomas are low grade, characterized by well-formed glands, small uniform nuclei image similar in appearance to benign luminal cells image, and rare or absent mitoses.






About 1/2 of breast cancers are high grade and are identified by their lack of gland formation, large, bizarre, pleomorphic nuclei that vary in size and shape image, and numerous mitotic figures.


TERMINOLOGY


Abbreviations



  • Elston and Ellis modification of Scarff-Bloom-Richardson histologic grading (MSBR)


Synonyms



  • Elston and Ellis grading


  • Modified Bloom-Richardson grade


  • Nottingham combined histologic grade


INTRODUCTION


Grade and Breast Cancer



  • MSBR is most widely used system for breast tumor grading



    • Recommended by College of American Pathologists, American Joint Committee on Cancer, and European Commission Working Group on Breast Screening Pathology


  • Grading divides breast cancers into groups that have different natural histories and biologic characteristics



    • MSBR grade describes features related to tumor differentiation and proliferation


    • Grade 1(well differentiated): 20% of cancers



      • Incidence higher in older &/or screened populations


    • Grade 2 (moderately differentiated): 30-35% of cancers


    • Grade 3 (poorly differentiated): 45-50% of cancers



      • Incidence higher in younger &/or unscreened populations


  • Other grading systems have been described but have not been as widely used or validated with as many studies as MSBR


Prognosis and Grade



  • Histologic grade is strongly correlated with breast cancer-specific survival and disease-free survival


  • Many clinical studies have validated and confirmed important prognostic significance of tumor grade



    • Significant association between grade and survival holds true for different tumor subgroups



      • Tumor size (pT1a, pT1b, pT1c, and pT2)


      • Lymph node stages (pN0, pN1, and pN2)


    • Grade correlated with overall length of survival regardless of clinical stage


ETIOLOGY/PATHOGENESIS


Grade and Genomic Grade Index (GGI)



  • GGI was developed using gene expression profiling



    • 97 genes were found to be differentially expressed between low and high histologic grade carcinomas


    • Majority of genes are associated with cell cycle regulation and proliferation


    • Low and high GGI strongly associated with disease-free and overall survival in ER-positive cancers



      • Low GGI found in luminal A cancers


      • High GGI found in luminal B, HER2, and basal-like cancers


    • Low and high GGI associated with histologic grade



      • Histologic grade 1: ˜ 85% low GGI


      • Histologic grade 3: ˜ 90% high GGI


  • GGI reclassified histologic grade 2 carcinomas into 2 groups



    • Approximately 2/3 were low GGI and had outcomes similar to other low-grade cancers


    • Approximately 1/3 were high GGI and had outcomes similar to other high-grade cancers


    • GGI has challenged clinical relevance of grade 2 category


  • GGI has helped validate histologic grade as important prognostic factor



    • Provides molecular basis underlying different grades of breast cancer


  • Simplified index using 4 genes associated with cell cycle progression and proliferation is determined
    using qRT-PCR (“PCR-GGI”) and can be used to analyze formalin fixed tissue



    • Genes used are MYBL2 (also used in Oncotype DX [Genomic Health; Redwood City, CA]), KPNA2 (also used in Mammaprint [Agendia; Irvine, CA]), CDC2, and CDC20


    • Results are similar to 97 gene assay


  • Histologic grade 2 carcinomas can also be subdivided by other measures of proliferation



    • Ki-67 (MIB-1) is positive in all cycling cells (i.e., all cells not in G0)



      • Histologic grade 1: 1-15% positive cells (mean ˜ 10%)


      • Histologic grade 2: 3-40% positive cells (mean ˜ 10%)


      • Histologic grade 3: 8-85% positive cells (mean ˜ 20%)


    • Grade 2 cancers can be divided into 2 groups based on Ki-67 scores; generally, cut-off point of 15% is used


Grade and Changes in DNA



  • Number and pattern of genomic copy number alterations differed significantly when stratified by grade



    • Average number of chromosomal changes increases with increasing grade


    • Low-grade carcinomas had fewer genomic alterations


  • Close correlation between DNA copy number and mRNA expression levels has been reported


  • Gene amplification may be common mechanism for increased gene expression in breast tumors



    • May help explain GGI


    • Genomic changes provide further validation for histologic grade as important prognostic factor


MICROSCOPIC FINDINGS


MSBR Grading



  • 3 features are evaluated separately; given scores of 1-3


  • Sum of scores determines final grade


MSBR (Sum of the Scores)

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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Histologic Grade

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