Table of Contents
Definition / general | Essential features | Prognostic factors | Uses by pathologists | Microscopic (histologic) description | Microscopic (histologic) images | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Roychowdhury M. Ki67. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainski67.html. Accessed January 25th, 2021.
Definition / general
- 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, nonhistone 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
Essential features
- Marker of cell proliferation
- Nuclear stain
- Considered a prognostic factor of breast cancer
- Included in Oncotype DX® (21 prospectively selected genes to predict risk of recurrence and chemotherapy benefit in node negative, ER+ women)
Prognostic factors
- Used for prognosis of relative responsiveness, resistance to chemotherapy or endocrine therapy and biomarker of treatment efficacy (high percentage reflects worse prognosis)
- High Ki67 predicts higher recurrence and progression in nonmuscle invasive bladder cancer than those with low Ki67 expression (Oncotarget 2017;8:100614)
- Superficial noninvasive papillary urothelial neoplasms of bladder show higher grade and recurrence with high Ki67 expression(Rev Col Bras Cir 2012;39:394)
- Chordoma: matrix poor phenotype and higher rate of metastasis associated with high Ki67 expression; also, increase in progression associated with higher Ki67 (Eur Spine J 2016;25:4016)
- Prostate cancer: High Ki67 associated with higher Gleason grade and worse prognosis (Br J Cancer 2013;108:271, Urol Ann 2015;7:488)
Uses by pathologists
- Nuclear stain; cytoplasmic staining is disregarded
- Distinguish benign / nonneoplastic 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-)
- Placenta: distinguish hyperplasia of intermediate trophoblast (Ki67+) from exaggerated placental site (Ki67-)
- Adrenocortical tumors: distinguish benign and malignant (Am J Surg Pathol 2002;26:1612)
- Grading:
- Invasive breast carcinoma: component of grading in addition to tubule formation and nuclear pleomorphism
- Breast phyllodes tumor: distinguish benign, borderline, malignant (low grade / high grade, Mod Pathol 2001;14:185)
- Classify / grade neuroendocrine tumors
- Sarcoma: component of grading in addition to necrosis and differentiation
- Part of staging for appendiceal carcinoid and grading for GI neuroendocrine tumors (Hum Pathol 2012;43:489)
- Poor prognostic factor (high levels) in many tumors:
- Bladder papillary urothelial neoplasm of low malignant potential (Cancer 2002;95:784)
- Chordoma (Arch Pathol Lab Med 2010;134:1170)
Microscopic (histologic) description
- Percentage of nuclei with positive staining in tumor cells are scored
- < 10%: low
- 10 - 20%: borderline
- > 20%: high (some variability in current literature regarding cut offs but > 20% is unanimaously considered high)
- Used in surrogate immunohistochemical classification for gene-expression profile based intrinsic breast cancer subtypes (low: luminal A; high: luminal B; higher: HER2; highest: basal-like) ( Hoda: Rosen's Diagnosis of Breast Pathology by Needle Core Biopsy, 4th Edition, 2017)
- May assist in distinguishing benign from malignant breast phyllodes tumor; may correlate with tumor grade and adverse prognosis in malignant phyllodes tumor (Mod Pathol 2001;14:185, Breast J 2002;8:38, Arch Pathol Lab Med 2006;130:1516)
- Grading for neuroendocrine tumors of tubular Gastrointestinal tract and pancreas: low
grade < 3%; intermediate grade 3 - 20%; high grade > 20%)
- Please note that there is a small subgroup of well differentiated neuroendocrine tumors that show > 20% Ki67 and are thus categorized as grade 3
- These tumors show prognosis intermediated between conventional grade 2 and grade 3 and are less chemosensitive than conventional grade 3 tumors ( Lloyd: WHO Classification of Tumours of Endocrine Organs, 4th Edition, 2017, Amin: AJCC Cancer Staging Manual, 8th Edition, 2018)
- Useful in histological grading of soft tissue sarcomas (World J Surg Oncol 2016;14:110)
- Useful in grading of meningiomas (J Clin Diagn Res 2016;10:EC15) and predicting risk of recurrence (Cureus 2017;9:e1820)
Microscopic (histologic) images
Contributed by Monika Roychowdhury, M.D., Kaveh Naemi, D.O., Cases #238, #237, #202, #194, AFIP images and Leica Microsystems
Images hosted on other servers:
Additional references
Board review style question #1
54 year old woman recently received the diagnosis of invasive ductal carcinoma for a right breast mass. Which of the prognostic markers below, if positive, suggest(s) aggressive behavior of the tumor?
- ER
- Ki67
- PR
- p63
Board review style answer #1