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Stains

Ki67 / MIB1


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 29 September 2013, last major update October 2012
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.

General
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● A marker of cell proliferation first described in 1983 (Int J Cancer 1983;31:13)
● Name derived from Kiel, Germany (city of origin) and the clone number in the 96 well plate (Wikipedia)
● Labile, non-histone nuclear protein expressed in G1, S, G2 and M phases of cell cycle, then rapidly catabolized at end of M phase and not detectable in G0 and early G1 cells (J Cell Physiol 2000;182:311)
● MIB1 is the IgG1 antibody against Ki67 for formalin-fixed, paraffin embedded tissue

Uses by pathologists
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● Nuclear stain; cytoplasmic staining is not important

Determine growth fraction of tumor

Distinguish benign/non-neoplastic and malignant/neoplastic lesions:
● Anus/cervix: HSIL (Ki67+) versus atrophy or normal (Ki67-, Am J Surg Pathol 2010;34:1449)
● Colonic polyp with cautery artifact: distinguish adenoma (Ki67+) from nonadenomatous polyp (Ki67-, Arch Pathol Lab Med 2007;131:1089)
● Lymph node, sentinel node biopsy: distinguish melanoma (Ki67+) from nevus cells (Ki67-, Am J Surg Pathol 2002;26:1351)
● Uterus: clear cell carcinoma (Ki67+) versus Arias-Stella reaction (Ki67-)

Classify lesions:
● Placenta: distinguish hyperplasia of intermediate trophoblast (Ki67+) from exaggerated placental site (Ki67-)

Tumor classification:
● Adrenocortical tumors: distinguish benign and malignant (Am J Surg Pathol 2002;26:1612)
● Breast phyllodes tumors: distinguish benign, borderline, malignant (low grade / high grade, Mod Pathol 2001;14:185)

Poor prognostic factor (high levels):
● Examples: bladder papillary urothelial neoplasm of low malignant potential (Cancer 2002;95:784). chordoma (Arch Pathol Lab Med 2010;134:1170)
● Part of staging for appendiceal carcinoid and grading for GI neuroendocrine tumors (Hum Pathol 2012;43:489)

Micro images
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Breast: hemangioma versus high grade angiosarcoma


Breast: invasive carcinoma


Breast: invasive carcinoma, basal-like subtype with high Ki67 index


Breast: invasive carcinoma, luminal A subtype with low Ki67 index (figure C)


Breast: phyllodes tumors (benign, borderline, malignant)


Cervix: adenocarcinoma in situ of endocervix


Colon: adenomatous versus nonadenomatous polyps


Kidney: malignant solitary fibrous tumor


Lymph node (normal): Ki67 nuclear staining highlights proliferating cells in the dark zone of the germinal center (bottom), away from the site of antigen entry at the top (see above image also) (AFIP 3rd Series Vol 14)


Lymph node (normal): Ki67 nuclear staining of the germinal center and paracortex of tonsil (AFIP 3rd Series Vol 14)


Lymph node: Burkitt lymphoma


Lymph node: Diffuse large B cell lymphoma


Pancreas: islet cell tumors (pancreatic endocrine tumors)


Skin: Spitz nevus


Skin: comparison of nevi versus melanoma


Skin: symplastic glomus tumor of toe


Small bowel: malignant GIST


Tonsil-normal (contributed by Leica Microsystems), shows intense nuclear staining of proliferating follicular cells

   
Urethra: clear cell adenocarcinoma

'  
Uterus (left to right): mid-proliferative endometrium, day 17 endometrium


Uterus: atypical polypoid adenomyoma (variable staining is typical)

Positive staining - normal
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● Placenta-early (cytotrophoblast: 25-50%, intermediate villous trophoblast: >90%, )

Positive staining - disease
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● High grade neoplasms, including Burkitt lymphoma, carcinoma in situ, invasive carcinomas (many), malignant phyllodes tumor (breast), sarcomas (many)
● Conjunctival Spitz nevus and squamous papilloma are Ki67+

Negative staining
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● Most benign or reactive lesions; nevi

End of Stains > Ki67


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