Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
ANNOUNCEMENT
Case Report
Case Series
Clinicodermoscopic Challenge
Clinicopathologic Challenge
Correspondence
Editorial
Faculty’s Forum
Image Correspondence
Innovations and Ideas
Letter to Editor
Original Article
Post Graduate Thesis Section
Quiz
Research Methodology and Publishing
Resident’s Forum
Review Article
Reviewers 2023
Short Communication
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
ANNOUNCEMENT
Case Report
Case Series
Clinicodermoscopic Challenge
Clinicopathologic Challenge
Correspondence
Editorial
Faculty’s Forum
Image Correspondence
Innovations and Ideas
Letter to Editor
Original Article
Post Graduate Thesis Section
Quiz
Research Methodology and Publishing
Resident’s Forum
Review Article
Reviewers 2023
Short Communication
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
ANNOUNCEMENT
Case Report
Case Series
Clinicodermoscopic Challenge
Clinicopathologic Challenge
Correspondence
Editorial
Faculty’s Forum
Image Correspondence
Innovations and Ideas
Letter to Editor
Original Article
Post Graduate Thesis Section
Quiz
Research Methodology and Publishing
Resident’s Forum
Review Article
Reviewers 2023
Short Communication
View/Download PDF

Translate this page into:

Letter to Editor
ARTICLE IN PRESS
doi:
10.25259/IJPGD_201_2024

Role of Ki67 Proliferative Index in Various Alopecia – A Pilot Study

Department of Dermatology, Venereology and Leprosy, Alluri Sitarama Raju Academy of Medical Sciences, Eluru, Andhra Pradesh, India.

*Corresponding author: Bandaru Divya Ravali, Department of Dermatology, Venereology and Leprosy, Alluri Sitarama Raju Academy of Medical Sciences, Asram Medical College, Eluru, Andhra Pradesh, India. divyaravalib@gmail.com

Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Divya Ravali B, Thatavarthi NB, Praveen Kumar Raju DV, Subba Rao D. Role of Ki67 Proliferative Index in Various Alopecia – A Pilot Study. Indian J Postgrad Dermatol. doi: 10.25259/IJPGD_201_2024

Dear Editor,

Diffuse alopecia presents significant challenges in dermatology, especially in women. Its main causes – female androgenetic alopecia (AGA), chronic telogen effluvium and diffuse alopecia areata (AA) – can exhibit similar signs, complicating diagnosis. Telogen effluvium typically occurs 2–3 months after triggers like childbirth or surgery, though triggers may be unclear. Early-stage AGA and diffuse AA can lack obvious signs, further complicating diagnosis. When clinical evaluation is difficult, tools such as trichoscopy, scalp biopsy and immunohistochemistry can help differentiate these conditions. Immunohistochemical techniques are increasingly valuable in diagnosing various skin disorders.

The Ki-67 protein was first identified using a monoclonal antibody developed from Hodgkin lymphoma cell line L428.[1] Ki67 is a nuclear protein that indicates cellular proliferation, predominantly expressed during the anagen phase of hair follicles, reflecting active regeneration.[2] Increased Ki67 levels are associated with hair growth, allowing researchers to differentiate between types of alopecia, such as AGA and telogen effluvium, where elevated levels suggest active growth and lower levels indicate disrupted hair cycling.

In AGA, reduced Ki67 expression in hair follicles indicates decreased proliferation and impaired anagen activation, resulting in thinner hair. In telogen effluvium, Ki67 serves as a marker for recovery, with higher levels suggesting a return to the anagen phase. AA shows diminished Ki67 binding, indicating suppressed keratinocyte proliferation.[3] In discoid lupus erythematosus, T-lymphocytic infiltrate affects hair follicles, with apoptotic keratinocytes exhibiting abnormal Ki67, p53 and bcl-2 expression.[4] In addition, Ki67 serves as a biomarker for evaluating treatment efficacy in hair loss therapies. Investigating Ki67 enhances our understanding of hair follicle biology and may lead to targeted therapies for hair regeneration, making it a valuable tool in both clinical and research contexts.

In this cross-sectional pilot study, we collected scalp biopsies from patients with hair disorders – AGA, telogen effluvium, AA, lichen planopilaris and discoid lupus erythematosus (diagnosed clinically and with biopsy) – over 2 months, alongside control subjects. Inclusion criteria required a diagnosis confirmed by biopsy, adults above 18 years, informed consent and no recent treatments (e.g. corticosteroids) which affect hair growth for 3 months before enrolment. Exclusion criteria included other dermatological conditions affecting hair growth, hair restoration surgeries, infections of scalp, pregnancy, lactation and non-compliance. After ethics approval, scalp biopsies from 30 patients were fixed, paraffin-embedded, cut into 3–4 µm sections, stained with hematoxylin and eosin for routine histopathological examination and subjected to Ki67 immunohistochemistry using heat-induced epitope retrieval to assess Ki67 positivity in the outer root sheath of hair follicles.[3]

A total of 30 patients aged 15–55 years participated in the study, with a mean age of 33.6 ± 9.84 years; the most common age group was 26–35 years [Table 1]. Among the participants, 16 were male (56.6%) and 14 were female (43.4%). The mean number of Ki67-immunoreactive cells per hair follicle for each group was as follows: Control group: 33.8 ± 4.48, AA: 17.8 ± 2.6, chronic telogen effluvium: 10.8 ± 1.96, AGA: 4.3 ± 1.67, lichen planopilaris: 1.5 ± 1.07 and discoid lupus erythematosus: 1 ± 0.95 [Table 2]. Analysis of variance (ANOVA) analysis showed a significant difference in the mean number of Ki67-immunoreactive cells among the six groups (P = 0.00001).

Table 1: Age distribution.
Age group (10-year interval) No. of patients Percentage
15–25 5 16.66
26–35 14 46.66
36–45 7 23.33
46–55 4 13.33
Total 30 100
Table 2: Comparison of the mean Ki-67 immunoreactive cells per hair follicle in each section across different disorders, along with their respective standard deviations.
Disorder Mean Ki-67 Immunoreactive cells per follicle in each section Standard deviation
Control 33.8 4.48
Alopecia areata 17.8 2.66
Chronic telogen effluvium 10.8 1.96
Androgenetic alopecia 4.3 1.67
Lichen planopilaris 1.5 1.07
Discoid lupus erythematosus 1 0.95

In our study, Ki-67 immunoreactivity was noted in the outer layer of hair follicles, especially at the hair bulb. Diseased scalp follicles had significantly lower Ki67 levels than controls, with telogen effluvium at 10.8 ± 1.96 cells and AGA at 4.3 ± 1.67 cells. AGA showed lower Ki-67 positivity than chronic telogen effluvium, while discoid lupus erythematosus and lichen planopilaris had the least. ANOVA revealed significant differences in Ki67 levels among the six groups (P = 0.00001), highlighting its potential to differentiate hair disorders based on proliferation.

Ashrafuzzaman et al. reported a significant decrease in Ki-67-immunoreactive cells in AA and AGA compared to controls, indicating reduced proliferative activity.[5] Our study found similar decreases in Ki67 positivity. Van Baar et al. also noted reduced Ki-67 binding in anagen hair follicles in AA, emphasizing its role in assessing hair follicle proliferation.[3]

Limitations include a small sample size that may limit generalizability, high costs of Ki-67 immunohistochemical analyses hindering larger studies and variability in staining techniques that can affect measurement accuracy and reproducibility.

This study compared the growth fraction in keratinocyte populations of normal and diseased hair follicles using Ki67. We found subtle differences in proliferation among disorders, especially between AGA and chronic telogen effluvium. While Ki67 provides insights into proliferation, its utility in distinguishing specific disorders may be limited. Larger studies are needed to validate these findings and explore additional markers for improved diagnostic accuracy and management of hair disorders. Further research is essential to assess the clinical utility of Ki67 immunohistochemistry.

Ethical approval

The research/study approved by the Institutional Review Board at ASRAMS BHR Ethics Committee, number ASRAMS BHR-EC/Approval No. 165/2023, dated 25 August 2023.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Financial support and sponsorship

Nil.

References

  1. , , , , . The Intrinsically Disorderly Story of Ki-67. Open Biol. 2021;11:210120.
    [CrossRef] [PubMed] [Google Scholar]
  2. , . Comparative Evaluation of the Clinical Efficacy of PRP-Therapy, Minoxidil, and their Combination with Immunohistochemical Study of the Dynamics of Cell Proliferation in the Treatment of Men with Androgenetic Alopecia. Int J Mol Sci. 2020;21:6516.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , , , . Abnormal Expression of Ki-67 Antigen in Hair Follicle of Alopecia Areata. Acta Derm Venereol. 1992;72:161-4.
    [CrossRef] [PubMed] [Google Scholar]
  4. , . Immunohistochemistry: Relevance in Dermatology. Indian J Dermatol. 2011;56:629-40.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , . Potential Involvement of the Stem Cell Factor Receptor c-kit in Alopecia Areata and Androgenetic Alopecia: Histopathological, Immunohistochemical, and Semiquantitative Investigations. Acta Histochem Cytochem. 2010;43:9-17.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views
447

PDF downloads
33
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections