Stains & molecular markers
Ki67 / MIB1

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Monika Roychowdhury, M.D.

Minor changes: 12 April 2021

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PubMed Search: Ki67[TI] pathology[TIAB] stain

Monika Roychowdhury, M.D.
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Cite this page: Roychowdhury M. Ki67. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainski67.html. Accessed April 18th, 2021.
Definition / general
  • Marker of cell proliferation first described in 1983 (Int J Cancer 1983;31:13)
  • 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)
Essential features
  • Marker of cell proliferation
  • Nuclear stain; cytoplasmic staining is disregarded
  • Used to help differentiate between benign versus malignant and increasingly used to grade various tumors (e.g. neuroendocrine tumors, pituitary tumor, schwannoma, meningioma, sarcoma, etc.) or dysplasia (cervical intraepithelial neoplasia, anal intraepithelial neoplasia, dysplasia arising in Barrett, etc.)
  • Used to determine prognosis of breast cancer, bladder cancer, prostate cancer and chordoma
Terminology
  • MIB1 (MIB1 is the IgG1 antibody against Ki67 for formalin fixed, paraffin embedded tissue)
Pathophysiology
  • MIB1 is a monoclonal antibody raised against a recombinant part of the Ki67 antigen
  • Both MIB1 and polyclonal anti-Ki67 antibody recognize the Ki67 antigen in fixed material
Clinical features
  • In general, increased in most malignant and inflammatory conditions but degree may differ
  • Used to grade various tumors, distinguish between differential diagnosis and predict prognosis
Interpretation
  • Nuclear staining
  • Percentage of nuclei with positive staining in tumor cells is scored
  • For dysplasia, thickness of epithelium / location of cells showing positive Ki67 staining is graded
Uses by pathologists
Prognostic factors
  • High Ki67 proliferative index used as an adverse prognostic marker for breast cancer, bladder cancer, prostate cancer, chordoma
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Monika Roychowdhury, M.D., Kaveh Naemi, D.O., Cases #238, #237, #202, #194, AFIP images and Leica Microsystems
Invasive ductal carcinoma breast

Invasive ductal carcinoma breast

Invasive ductal carcinoma (Ki67)

Invasive ductal carcinoma (Ki67)

Cervix low grade squamous dysplasia Cervix low grade squamous dysplasia

Cervix low grade squamous dysplasia

Cervix high grade squamous dysplasia Cervix high grade squamous dysplasia

Cervix high grade squamous dysplasia


Lung typical carcinoid Lung typical carcinoid

Lung typical carcinoid

Lung small cell carcinoma Lung small cell carcinoma

Lung small cell carcinoma

Stomach well differentiated neuroendocrine tumor Stomach well differentiated neuroendocrine tumor

Stomach well differentiated neuroendocrine tumor


Brain diffuse large B cell lymphoma Brain diffuse large B cell lymphoma

Brain diffuse large B cell lymphoma

Lymph node, Burkitt lymphoma

Lymph node, Burkitt lymphoma

Cervix, adenocarcinoma in situ, endocervix

Cervix, adenocarcinoma in situ, endocervix

Urethra, clear cell adenocarcinoma Urethra, clear cell adenocarcinoma

Urethra, clear cell adenocarcinoma


Lymph node, normal Lymph node, normal

Lymph node, normal

Positive staining - normal
  • Most tissues have baseline positive staining 0 - 1% as a very low proliferative index
Positive staining - disease
  • Cervical / anal dysplasia (mild dysplasia: lower 33% of epithelium shows increased Ki67 staining; moderate dysplasia: 66% of epithelium shows increased Ki67 staining; severe dysplasia / CIS: full thickness of epithelium shows increased Ki67 staining)
  • Gastrointestinal neuroendocrine tumors (low grade: < 3%; intermediate grade: 3 - 20%; high grade: > 20%)
  • Lung neuroendocrine tumors (typical carcinoid: up to 5%; atypical carcinoid: up to 20 - 25%; large cell neuroendocrine carcinoma: 40 - 80%; small cell lung carcinoma: 50 - 100%) (Transl Lung Cancer Res 2017;6:513)
  • Meningioma: Ki67 (not a diagnostic criterion but is usually > 4% and goes up to 20% depending on grade - I, II or III)
  • Astrocytoma (astrocytoma: < 4%; anaplastic astrocytoma: 5 - 10%; glioblastoma: 15 - 20%) (Pathol Oncol Res 2006;12:143)
  • Bladder cancer prognosis (PLoS One 2016;11:e0158891)
  • Breast cancer prognosis, higher percentage associated with worse prognosis (cutoffs < 10%, 10 - 25%, > 25%) (Eur J Breast Health 2019;15:256)
Sample pathology report
  • Stomach, resection:
    • Well differentiated neuroendocrine tumor, 1.5 cm, surgical margins negative (see synoptic report)
    • Ki67 labeling index < 3%
  • Lung, right upper lobe, biopsy:
    • High grade neuroendocrine carcinoma, small cell carcinoma
    • Ki67 proliferative index > 90%
Board review style question #1
A 54 year old woman recently received the diagnosis of invasive ductal carcinoma for a right breast mass. Which of the prognostic markers below, if more than 30%, suggests aggressive behavior of the tumor?

  1. ER
  2. Ki67
  3. PR
  4. p63
Board review style answer #1
B. Ki67

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