Breast cancer: IHC classification. Mogens Vyberg Professor of Clinical Pathology Director of NordiQC Aalborg University Hospital, Aalborg, Denmark

Transcription

1 Breast cancer: IHC classification Mogens Vyberg Professor of Clinical Pathology Director of NordiQC Aalborg University Hospital, Aalborg, Denmark

2 Breast 2

3 Breast Actin 3

4 Breast markers for carcinoma diagnostics Unknown Primary Primary Breast GATA3 + - GCDFP Mammaglobin + - Estrogen receptor α (ER) + + Progesteron receptor (PR) - + HER2 - + Ki E-Cadherin / p CK5 / CK p63 / p Actin / Myosin - + Subclassification Diagnostic Prognostic/ predictive

5 GATA3 Transcription factor recognizing the G-A-T-A nucleotide sequences in target gene promoters, regulating genes involved in the development/maintenance of T-cells breast epithelium urothelium kidney skin trophoblast endothelia

6 GATA3 Transcription factor recognizing the G-A-T-A nucleotide sequences in target gene promoters, regulating genes involved in the development/maintenance of T-cells breast epithelium urothelium kidney skin trophoblast endothelia

7 GATA3 Transcription factor recognizing the G-A-T-A nucleotide sequences in target gene promoters, regulating genes involved in the development/maintenance of T-cells breast epithelium urothelium kidney skin trophoblast endothelia

8 GATA3 + Breast carcinoma Urothelial carcinoma Skin carcinoma (squam., bas., adnex) Yolk sac tumour Lobular breast carcinoma Urothelial carcinoma Miettinen et al. Am J Surg Pathol. 2014, 38:13-22.

9 GATA3 +/- Malignant mesothelioma Paraganglioma Chromophobe renal cell carc. Pancreas/biliary tract adenocarcinoma

10 SPYBYTE biopsy choledochus

11 SPYBYTE biopsy choledochus GATA3

12 GATA3 -/+ Non-skin squamous cell carc. Salivary gland carcinomas Adrenal cortical carcinoma Embryonal carcinoma -(+) Serous / endometrioid adenocarcinoma Colon / gastric adenocarcinoma Prostate adenocarcinoma Renal cell carcinoma (non-chrom.) Thyroid carcinoma Sarcomas - Endocrine neoplasms Malignant melanoma Seminoma

13 GCDFP-15 (gross cystic disease fluid protein 15) Prolactin induced glycoprotein of apocrine cells Adenocarcinomas Breast +/ Sweat gland +/ Salivary gland +/ Lung (+) Renal cell (+) Ovary (+) GCDFP-15 in sweat glands

14 GCDFP-15 Breast carcinomas

15 Gastric biopsies, 43 y ER GCDFP-15

16 GCDFP15 Optimal GCDFP15 Insufficient Low Ab conc. 2-layer detect. system

17 Mammaglobin Mammary-specific member of the uteroglobin family Adenocarcinomas Breast +/ Sweat gland +/ Salivary gland +/ Lung /+ Stomach, biliary, thyroid, ovary, endom. (+) Mammaglobin in breast

18 Mammaglobin Breast ductal carcinomas

19 61, Metastatic adenocarcinoma UPT in the eye lid

20 61, Metastatic adenocarcinoma UPT in the eye lid GCDFP-15

21 61, Metastatic adenocarcinoma UPT in the eye lid MAMMAGLOBIN

22 61, Metastatic adenocarcinoma UPT in the eye lid Primary male cancer excluded: Primary eye lid carcinoma - Moll s apocrine sweat gland

23 Estrogen receptor alpha Estrogen sensitive tissues: Breast Ovarium Fallopian tube Endo- and myometrium Uterine cervix Thyroid gland Pituitary gland Pancreas Sweat gland Salivary gland Prostate, Liver

24 Estrogen receptor alpha Adenocarcinomas Breast carcinoma +/ Ovarian (non-muc.) +/ Endometrial carc. +/ Cervix, lung, kidney, endocrine... /+ ERα Sica et al. APLM 132,1889,2008

25 Estrogen receptor alpha Lung adenocarcinomas ERα Sica et al. APLM 132,1889,2008

26 Estrogen receptor alpha: The influence of antibody selection ERα 92 lung adenocarcinomas ER+ ( 1% pos. cells) 1D5: 8% 6F11: 14% SP1: 27% Gomez-Fernandez et al. AIMM 2010;18:137

27 Scoring hormone receptors Allred Scoring System 27

28 Gándara-Cortes et al.

29 Change of cut-off from 10% to 1% 100% 100% 90% 80% 70% 60% biopsi unknown 50% 40% 30% 20% 10% 0% 0% % Lump 1-9% Mast 0% Danish Breast Cancer Cooperative Group

30 Gándara-Cortes et al. 70% + 41% 32% 10% 6% 11%

31 Luminal A: ER-positive, HER2-negative, Ki67- low and Luminal B: ER-positive, HER2-negative, Ki67> 14% or Luminal B: ER-positive, HER2-overexpressed or amplified, any Ki67 HER2-positive (non luminal): HER2 overexpressed or amplified and ER negative Triple-negative: ER-negative, (PR-negative), HER2-negative

32

33

34 34

35 NordiQC runs for HER2 IHC 35 CK7 Ampl. 3+ Ampl. 2+ Unampl. 2+ Unampl. 0 35

36

37

38 HER2 FISH HER2 GPA

39 Prognosis and proliferation Ki-67 39

40 Ki67 immunoassay Digital image analysis Clone SP6 concentrate Ventana platform Prolif.index 38 % Clone MM1 RTU Leica platform Prolif.index 12 %

41 Concentrate Mib1 as concentrate in optimized protocols on 3 platforms RTU

42 E-Cadherin and E-cadherin complex E-Cadherin and p120 From Dabbs J.D. et al. Am J Surg Pathol 2007, 31;

43 DCIS vs. LCIS E-Cadherin E-Cadherin 43

44 Collision carcinoma E-Cadherin 44

45

46 Lobular carcinoma E-cadherin loss

47 CK5 /CK14 Ductal hyperplasia vs. Ductal carcinoma in situ

48 Breast carcinoma - basal like CKHMW CK5/6 p63 48

49

50 Breast cancer: IHC classification Mogens Vyberg Professor of Clinical Pathology Director of NordiQC Aalborg University Hospital, Aalborg, Denmark