1. Gem Wu
吳懷玨 整理
2017/11/3
【病理】
免疫組織化學染色
Immunohistochemistry (IHC)

2. 看病理報告，完全不知道在說什麼，怎麼辦?
“CK7-/CK20+, TTF1-, CK17+…”

3. Pathologist’s H&E
is like the clinician’s H&P
Special studies like IHC
could be performed

4. Purpose of IHC
Purpose 目的 Example
Classification of tumors
區分腫瘤
carcinoma vs. lymphoma
B cell vs. T cell lymphoma
in situ lesions vs. invasive carcinomas
原位癌 或 侵襲癌
myoepithelial markers in breast cancers
basal cell markers in prostate
Prognostic factors
預後因子
Ki-67 in glioblastomas (GBM)
Predictive factors for specific therapy
標靶治療效果預測
c-KIT
ER, PR, HER2/neu
Identification of extracellular material
胞外物質
β-2 microglobulin amyloid
Identification of infectious agents
傳染性物質
CMV or HSV
[整理自: Susan Lester, Manual of Surgical Pathology 3e]

5. IHC applications -1
Application Tumor markers
Histological typing Carcinoma Cytokeratin
Sarcoma Vimentin
Glial tumor GFAP
Melanoma HMB-45,
Melan-A
Lymphoma LCA
Differentiation
Sarcoma
Liposarcoma S-100
Angiosarcoma CD31
factor VIII
Leiomyo-
sarcoma
SMA
Rhabdomyo-
sarcoma
Desmin
[Note from Ming-Yuan Lee, M.D.’s Lecture]
Application Tumor/site Markers
Organ specific Thyroid Thyroglobulin
prostate PSA
Lung, thyroid TTF-1
Sub-
classification
B-cell CD20, CD79a
T-cell CD3, CD5, CD43
NK cell CD56
Myeloid
series
MPO
Infectious
disease
- CMV
Lung PJP

6. IHC applications -2
Application Tumor markers
Secretion or
tumor
products
Adenocarcinoma CEA
Neuroendocrine tumor Synaptophysin,
insulin, gastrin
Breast tumor BRST-2
HCC α-fetoprotein,
Hepar-1
Choriocarcinoma β-HCG
Yolk sac tumor or
embryonal carcinoma
α-fetoprotein
Biological
factors for
prognostic
values
(Proliferation index) Ki-67
(anti-apoptotic factor) Bcl-2
(Poor prognosis) Her2
[Note from Ming-Yuan Lee, M.D.’s Lecture]
Application Treatment marker
s
Therapy Tamoxifen ER/PR
Herceptin HER2
Gleevec CD117
Erlotinib
(Tarceva®)
EGFR
Pem-
brolizumab
PD-L1
不同的organ, standard不同
Lymphoma 50% Ki-67+可能只是moderate,
但breast可能就是high

7. Tumor sites
各別來看看不同地方的carcinoma可能會有哪些IHC

8. Carcinoma: CK7, CK20
CK7+ CK20+
Lung adenoCA
Breast ductal, lobular CA
Ovary, uterus, cervix
colorectal adenoCA
CK7+/CK20+
Transitional cell CA
Pancreatic cancer
cholangiocarcinoma
CK7-/CK20-
SqCC (lung, HEENT), lung
Small cell CA, HCC, RCC,
prostate, adrenal cortical CA
thyroid
Ligament of
Treitz

9. Organ specific markers of carcinoma
Breast Cancer – IHC有助規劃Treatment
IHC result ER/PR HER2/neu
Positive 70-80% 15-20%
Borderline 5-10% 25-35%
Negative 20-30% 70%
[來自: Susan Lester, Manual of Surgical Pathology 3e]
HER2/neu+ → 可用Herceptin治療
↓ HER2/neu+用IHC(左)與ISH(右)
Other markers: (如果不確定可以三個一起染)
GCDFP-15, mammaglobin, GATA3…
[Arch Pathol Lab Med. 2016;140:508–523; doi: 10.5858/arpa.2015-0173-CP)]

10. Organ specific markers of carcinoma
Lung Cancer – IHC分辨不同類型
tumor CK7 CK20 TTF-1 P63 Chromogranin
Adenocarcinoma 90+% 10-40% 60-90% 10-40% <10%
Bronchioloalveolar
carcinoma — nonmucinous
90+% 10-40% 60-90% 60-90% <10%
Bronchioloalveolar
carcinoma — mucinous
60-90% 60-90% 10-40% <10%
Squamous cell carcinoma 10-40% <10% <10% 90+% <10%
Large cell carcinoma 60-90% 10-40% 40-60% 40-60% <10%
Small cell carcinoma 10-40% <10% 90+% <10% 40-60%
Carcinoid tumor 40-60% <10% 10-40% <10% 90+%
Metastatic colon carcinoma 90+% 10-40% <10% <10% <10%
Metastatic breast carcinoma 90+% <10% <10% <10% <10%
通常會染TTF-1來確認lung origin，但總有些例外…
[整理自: Susan Lester, Manual of Surgical Pathology 3e]
Neuroendocrine
tumor marker

11. Organ specific markers of carcinoma
GI tract Cancer v. GYN cancer – 確認origin
CDX2 is expressed in virtually 100% of colorectal adenocarcinomas.
(除了MSI – microsatellite unstable genotype外)
tumor CK7 CK20 MUC2 CDX2 WT-1
Stomach 60-90% 40-60% 40-60% 40-60% 40-60%
pancreas 90+% 60-90% 90+% 40-60% 40-60%
appendix 10-40% 90+% 90+% 90+% -
Colon <10% 90+% 60-90% 90+% 60-90%
Uterus 90+% 10-40% <10% 10-40% 40-60%
Ovary, serous 90+% 10-40% 10-40% 40-60% 60-90%
Ovary, mucinous 90+% 60-90% 10-40% 40-60% 10-40%
Breast, no special type (NST) 90+% <10% 10-40% <10% 10-40%
Breast, mucinous 90+% 10-40% 90+% - 60-90%
[整理自: Susan Lester, Manual of Surgical Pathology 3e]
1
2
3
4
5
6
PAX-8是Müllerian duct轉錄因子，因此許多GYN tumor會表現，也可以此區別mets的breast CA v. primary

12. Organ specific markers of carcinoma
Liver Cancer – 區分primary或metastasis
Hep-Par 1 Ab, arginase-1 比傳統的 α-FP更sensitive與specific for HCC
[圖來自: Susan Lester, Manual of Surgical Pathology 3e]
Hepatoplastoma Cholangiocarcinoma
? ?CK7+, AE1/AE3+,
keratin HMW+
一般來說，liver primary cancer會有CAM5.2+, CK20-, CEA+
CD10+
cirrhosis (65-90%)
↓ HBV+ (50%)
α-FP+, HEP+
CDX2+
HEP+
[Arch Pathol Lab Med. 2016;140:508–523; doi: 10.5858/arpa.2015-0173-CP)]

13. Other markers for carcinomas
Prostate CA
(NKX3.1)
(PSA)
TCC
(GATA3)
(Uroplakin)
(p63, p40)
RCC
(PAX2)
(PAX8)
Thyroid papillary,
follicular CA
(Thyroglobulin)
(PAX8)
Most thyroid CA
(TTF-1)
adrenal CA
(inhibin-α)
(Melan-A)
(Steroidogenic
factor 1)
SqCC (not organ specific)
(p63+, p40+)
(CK5)[Arch Pathol Lab Med. 2016;140:508–523; doi: 10.5858/arpa.2015-0173-CP)]

14. 一些小練習
要開始囉

15. Case 1
• Ex-smoker
• Biopsy from
left lower
lobe of lung
• w/ Hx of
biopsy
proven colon
CA
• Dx?
CK20+++H&E
CDX2+++ TTF1-
(CK7-)
[Arch Pathol Lab Med. 2016;140:508–523;
doi: 10.5858/arpa.2015-0173-CP)]

16. [CASE2]
63M, no known primary carcinoma, CCx cervical
lymphadenopathy, this is the result of FNA of the node:
CK7-, CK20-, TTF1-, CDX2-, PSA+++, Villin-. Dx?
[CASE3]
73F, hx hysterectomy for unknown reason, CCx retroperitoneal
lymphadenopathy, image showed left pelvic sidewall mass probably
residual ovary. this is the FNA result:
ER++, WT++, PAX+++, CK7+++, CK20-, GATA3-, CDX2-, p63-. Dx?
[Arch Pathol Lab Med. 2016;140:508–523; doi: 10.5858/arpa.2015-0173-CP)]

17. Lymphoma太難QAQ
請更專業的來吧…

18. 最後幾點原則
1. 看不懂報告，自己查資料也不懂的話，還是要請教病理專業！
2. IHC不是絕對，positive與negative的出現也有其機率，不能妄
下診斷。
3. 遇到奇怪的marker表現，或異常不表現，還是可以去survey一
下其他器官。小心駛得萬年船。