ONKOLOGIA: Onko metastasoineen rintasyövän diagostiikka helppoa? Ei ole.

. 2021 Jan;34(Suppl 1):62-77.

doi: 10.1038/s41379-020-00697-3. Epub 2020 Oct 27. 

https://www.modernpathology.org/article/S0893-3952(22)00365-9/fulltext 

Novel uses of immunohistochemistry in breast pathology: interpretation and pitfalls

Ashley Cimino-Mathews  ¹

Affiliations PMID: 33110239 DOI: 10.1038/s41379-020-00697-3 Free article

 Abstract

Immunohistochemistry is an essential component of diagnostic breast pathology. The emergence of novel assays and applications is accompanied by new interpretation criteria and potential pitfalls. Immunohistochemistry assists in supporting breast origin for primary or metastatic carcinomas and identifying non-mammary metastases to the breast; however, no single immunostain is perfectly sensitive nor specific. GATA3 and Sox10 are particularly useful immunostains to identify triple negative breast carcinoma, which are often negative for other markers of mammary differentiation. Sox10 labeling is a major potential diagnostic pitfall, as Sox10 and S-100 label both triple negative breast carcinoma and metastatic melanoma; a pan-cytokeratin immunostain should always be included for this differential diagnosis.

 Novel immunohistochemistry serves as surrogates for the molecular alterations unique to several of special-type breast carcinomas, including the use of MYB in adenoid cystic carcinoma, pan-TRK in secretory carcinoma, and mutant IDH2 in tall cell carcinoma with reversed polarity (TCCRP). In addition, PD-L1 immunohistochemistry is an emerging, albeit imperfect, biomarker for breast cancer immunotherapy, with different assay parameters and scoring criteria in breast carcinoma compared to other tumor types. The expanding repertoire of novel immunohistochemistry provides additional diagnostic tools and biomarkers that improve diagnostic breast pathology and patient care. 

Table 1Targeted immunopanels and pitfalls when determining cancer site of origin.

Primary tumor	Pertinent positive immunohistochemistry	Pertinent negative immunohistochemistry	Potential pitfalls
ER+ breast cancer	ER, GCDFP, MMGB, GATA3, CK7	CK20, TTF-1, CDX2
ER− breast cancer	GATA3, Sox10, cytokeratin	ER, GCDFP, MMGB	Melanoma is S-100+/Sox10+
Melanoma	S-100, Sox10, HMB45, Melan A, MITF	Cytokeratin	TNBC can be S-100+/Sox10+
Lung adenocarcinoma	TTF-1, Napsin A		Can be GATA3+/ER+
High-grade serous	ER, WT-1, PAX8	GATA3, GCDFP	Breast cancer can be WT-1+
Prostate cancer	PSA, P501S, NKX3.1	ER, GATA3	ILC and male IDC can be NXK3.1+
GI adenocarcinoma	CDX2, CK20, or CK7	DPC4 (subset)	Can be GATA3+

 

ER estrogen receptor,

 GCDFP gross cystic disease fluid protein,

 GI gastrointestinal,

 IDC invasive ductal carcinoma, 

ILC invasive lobular carcinoma, 

MMGB mammaglobin, 

TNBC triple negative breast carcinoma.

• Open table in a new tab

 GATA3  

Muistiin: GATA-domeenin omaavia  Znf-proteiineja on  toistakymmentä ja kertaan  tänään 4 ensimmäistä )  Kaikki 15 GATAD sinkkisormiproteiinia ovat transkriptiofaktoreita TFs Matteo Cassandrin antaman luettelon mukaan.

Sox-10

cytokeratin

S-100 

PAX8

NKX3.1

CK20

CK7 

TTF1

CDX2

Napsin A

WT-1, WILMS Tumor -1

 DPC-4

GATA3 (Koska tämä on ZNF sinkkisormiproteiini GATAD tyyppiä, GATA-domainin sisältävä, katson erikseen  GATAD ryhmän znf proteiinit tänään 7.12. 2023)

GATA3 is a transcription factor involved in the differentiation of many tissue types, including the breast luminal epithelial cells [6], and GATA3 is linked to ER signaling in breast cancer [5]. GATA3 is a superior marker for ER⁺ breast carcinoma than GCDFP or mammaglobin, with labeling consistently reported in over 90% of ER⁺ breast carcinomas [3,4,5,7]. In addition, GATA3 is more sensitive for triple negative breast carcinomas, with labeling commonly reported in over 50–83% [4,5,7,8], and has greater utility than GCDFP or mammaglobin in this context. GATA3 also displays nuclear rather than cytoplasmic labeling (Fig. 2), which can be easier to interpret, and shows strong and diffuse labeling in nearly all ER⁺ breast carcinomas. GATA3 also labels lymphocytes, which serve as useful internal controls in GATA3⁻ tumors (Fig. 3). GATA3 is not specific for breast carcinoma, however, and also labels urothelial carcinomas, squamous cell carcinomas, and mesotheliomas, with labeling in smaller numbers of pancreatic adenocarcinomas, lung adenocarcinomas, and others [5,7], as discussed below.