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Year : 2018  |  Volume : 61  |  Issue : 2  |  Page : 225-227
Expression of E-cadherin, syndecan 1, Ki-67, and maintenance minichromosome 3 in tissue lesions of actinic prurigo obtained by incisional biopsy


1 Department of Dermatology, “Dr. Manuel Gea González” General Hospital, Mexico City, Mexico
2 Faculty of Dentistry, University of the Republic, Montevideo, Uruguay
3 Department of Stomatology, Institute of Biomedical Sciences, Autonomous University of Ciudad Juarez, Chihuahua, Mexico

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Date of Web Publication20-Apr-2018
 

   Abstract 


Actinic prurigo (AP) is an idiopathic photodermatosis; the initial manifestations usually occur during the first decades of life but can appear at any age. Cases are usually diagnosed late once the lesions have exacerbated; due to the extensive involvement of the vermilion border and the etiology, it has been confused with and related to a potentially malignant process. Syndecan-1 and E-cadherin were positive in the epidermis, with moderate-to-intense staining in 100% of samples. Ki67 and MCM3 were expressed in the lower third of the epidermis and showed greater immunolabeling in samples that contained lymphoid follicles (Ki 67: epidermis [17.7% ± 6.79%] and dermis [7.73% ± 6.69%]; MCM3: epidermis [22.92% ± 10.12%] and dermis [6.13% ± 6.27%]). In conclusión AP is a disease in which there is no evidence that the lesions are potentially cancerous. AP cheilitis should not be confused with actinic cheilitis because they are separate entities.

Keywords: Actinic prurigo, histopathological characteristics, Immunohistochemistry panel

How to cite this article:
Mancheno-Valencia A, Bologna-Molina RE, Toussaint-Caire S, Vega-Memije ME, Cuevas-González JC. Expression of E-cadherin, syndecan 1, Ki-67, and maintenance minichromosome 3 in tissue lesions of actinic prurigo obtained by incisional biopsy. Indian J Pathol Microbiol 2018;61:225-7

How to cite this URL:
Mancheno-Valencia A, Bologna-Molina RE, Toussaint-Caire S, Vega-Memije ME, Cuevas-González JC. Expression of E-cadherin, syndecan 1, Ki-67, and maintenance minichromosome 3 in tissue lesions of actinic prurigo obtained by incisional biopsy. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 Apr 6];61:225-7. Available from: http://www.ijpmonline.org/text.asp?2018/61/2/225/230560





   Introduction Top


Actinic prurigo (AP) is an idiopathic photodermatosis that affects the skin and labial and conjunctival mucosa. Miscegenation is a significant racial factor that is linked to human leukocyte antigen (HLA), particularly the HLA-DR4 allele, which varies between populations. In Mexico, 90%–92.8% of patients with AP have this allele (HLA-DRB1*0407 is the most frequent subtype [60%–80%]).[1],[2],[3]

The initial manifestations of AP usually occur during the first decades of life but can appear at any age. Cases are usually diagnosed late once the lesions have exacerbated, AP preferentially affects women at a 2:1 ratio and persons with dark phototypes (Fitzpatrick IV and V classification).[4],[5],[6],[7]

The lesions develop after sun exposure, usually as papules, macules, excoriations, serohematous scabs, areas of lichenification, scars, hypo- or residual hyperpigmentation, edema, cracks, fissures, and ulcers on the vermilion border lip. These signs constitute AP cheilitis, which has an acute phase with exudative lesions and adherent yellow scabs and a chronic phase, in which there is scaling and xerosis.[8] Due to the extensive involvement of the vermilion border and the etiology that is associated with sun exposure, it has been confused with and related to a potentially malignant process.

Common histopathological features of AP are hyperkeratosis, parakeratosis, acanthosis, thickening of the basement membrane, perivascular inflammatory, lymphoid follicles, or nodular lymphocytic infiltrate, as well as eosinophils, mast cells, and angiogenesis.[9]

Syndecan 1 is a cell surface proteoglycan and is an active component of the molecular adhesion between cells and the extracellular matrix; its loss of expression is associated with malignant transformation and is directly related to the advanced stages of the neoplasia. Cadherins mediate the adhesion between cells.

Maintenance minichromosomes (MCMs) are a family of eight proteins – MCM2-MCM-7 and MCM-10 – which regulate the S phase of the cell cycle.[10] MCM3 and Ki67 are important markers of cell proliferation. Thus, the expression of these markers was examined to increase our understanding of the pathophysiology of AP and demonstrate that this disease does not have malignant potential.


   Materials and Methods Top


This descriptive study included paraffin-embedded tissues (from lip and skin incisional biopsy) in patients with a confirmed diagnosis of AP (n = 24). Two dermatopathologists who were experts in this area assessed all cases. Hematoxylin and eosin staining was used to analyze the histopathological characteristics of the samples, obtained from the patient. Sociodemographic data, such as age, sex, and biopsy site, were collected.

Two micron sections were performed and stained by immunohistochemistry (monoclonal primary antibodies: Dako syndecan-1 (CD-138), clone: Ml15, 1:100 dilution; Dako E-cadherin, clone: NCH-38, 1:100 Ki-67, Dako, clone: MIB 1, 1:50 dilution; and MCM3, Abcam Cambridge UK, clone: ab97282, 1:100 dilution were used); the tissues were counterstained with Mayer's hematoxylin.

Expression was evaluated semi-quantitatively in five fields per case at ×400 [Table 1] and was photographed with an Olympus C-7070 digital camera.
Table 1: Categorization of antibody expression

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   Results Top


Of the 24 cases in the study, n = 12, 50% were female patients, and all were diagnosed with AP. The mean evolution of the disease was 11.25 years, and the most frequent biopsy site was the lip n = 20, 83.3% and skin n = 4, 16.6%.

Syndecan-1 and E-cadherin were positive in the epidermis, with moderate-to-intense staining in 100% of samples. Syndecan-1 was expressed in the dermis in 25% of cases due to the presence of plasma cells; E-cadherin was negative at this site [Table 2].
Table 2: Expression of adhesion molecules in epidermis and dermis in actinic prurigo samples

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Ki67 and MCM3 were expressed in the lower third of the epidermis, and in the dermis, these markers showed greater immunolabeling in samples that contained lymphoid follicles (Ki 67: epidermis [17.7% ± 6.79%] and dermis [7.73% ± 6.69%]; MCM3: epidermis [22.92% ± 10.12%] and dermis [6.13% ± 6.27%]). [Figure 1] and [Table 3] show the immunohistochemistry results by sex and location.
Figure 1: Expression of E-cadherin and syndecan-1, respectively, in the various strata of the epidermis in cases of actinic prurigo (a, [×100] and b, [×400]). Ki-67 and MCM3, respectively, in the lower third of the epidermis (c and d, ×400)

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Table 3: Expression of markers according to sex and site of biopsy

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   Discussion Top


AP is a condition that is diagnosed late. In a study at General Hospital Dr. Manuel Gea González, where the sociodemographic profiles of such patients have been reported for the past 20 years, the average time of making the diagnosis was 8.78 years after the initial lesions had appeared [2] versus 11.25 years in the current study. Thus, if the diagnosis is established in a timely manner, it is possible to avoid the appearance of its clinical characteristics, before they exacerbate in the chronic phase.

Fifty percent of our cohort was male, which might be due to the small sample. Furthermore, 83.3% of biopsies were taken from the lip, which is consistent with it being the preferred site for histopathological studies.

MCM is a cell cycle regulator; they are expressed at high levels during proliferation and degrade in the resting state and senescence and are thus used as markers of cell proliferation.[10] MCMs are also positive in cells without alteration (located in the basal stratum) that are in the normal phase of proliferation but at lower levels compared with neoplastic cells, which serve as a reference during the evaluation.[11] Our results are consistent with the literature; MCM-3 positivity was observed in the lower third of the epidermis and in the dermis in cases that had lymphoid follicles.

Ki-67 is a nuclear protein that is present in all active phases of the cell cycle, except G0 and quiescence, and is used to measure the fraction of healthy and neoplastic tissues that is growing.[12] Arrese et al. studied the histopathology of 20 Mexican miscegenated patients who were diagnosed with AP using immunohistochemical panels and observed that Ki-67 was positive in 34.5% of epidermal cells and in the strata basale and spinosum.[6] We also noted positivity of Ki-67 in the basal stratum in 17.7% of cases. Thus, based on MCM-3 and Ki-67 immunolabeling, cell proliferation is not increased in this disease.

Cadherins are a family of transmembrane type 1 proteins that mediate Ca 2+-dependent cell–cell adhesion in epithelial tissues maintain cell polarity and adhesion in tissues. Its epithelial expression decreases in potentially cancerous lesions.[13] Syndecan members form a family of cell surface proteoglycans that interact with several molecular effectors of the extracellular matrix and growth factors. Syndecan-1 is found primarily in epithelial cells and mediates cell adhesion with various molecules of the extracellular matrix.[14] In our AP tissues, syndecan-1 and E-cadherin were positive throughout the epidermal thickness in 100% of cases, confirming that there is no loss of cell adhesion in this disease and thus suggesting a malignant process.


   Conclusions Top


AP is a disease in which there is no evidence that the lesions are potentially cancerous. AP cheilitis should not be confused with actinic cheilitis because they are separate entities with regard to their clinical and histopathological characteristics and their potential for malignancy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Vera Izaguirre DS, Zuloaga Salcedo S, González Sánchez PC, Sánchez Lara K, Chávez Tapia N, Hojyo Tomoka MT, et al. Actinic prurigo: A case-control study of risk factors. Int J Dermatol 2014; 53:1080-5.  Back to cited text no. 1
    
2.
Cuevas-González JC, Rodríguez-Lobato E, Mancheno-Valencia A, Hojyo-Tomoka MT, Domínguez-Soto L, Vega-Memije ME. Actinic Prurigo; demographic profile of the last 20 years in the dermatology division of the general hospital Dr. Manuel Gea González in Mexico City. Dermatol Rev Mex 2014; 58:508-13.  Back to cited text no. 2
    
3.
Granados-Arriola J, Domínguez-Soto L. Immunogenetics of actinic prurigo in Mexican patients. Dermatol Rev Mex 1993;37:314-5.  Back to cited text no. 3
    
4.
Hojyo-Tomoka MT, Vega-Memije ME, Cortes-Franco R, Domínguez-Soto L. Diagnosis and treatment of actinic prurigo. Dermatol Ther 2003;16:40-4.  Back to cited text no. 4
    
5.
Hojyo-Tomoka T, Vega-Memije E, Granados J, Flores O, Cortés-Franco R, Teixeira F, et al. Actinic prurigo: An update. Int J Dermatol 1995;34:380-4.  Back to cited text no. 5
    
6.
Arrese JE, Dominguez-Soto L, Hojyo-Tomoka MT, Vega-Memije E, Cortés-Franco R, Guevara E, et al. Effectors of inflammation in actinic prurigo. J Am Acad Dermatol 2001;44:957-61.  Back to cited text no. 6
    
7.
Sachdeva S. Fitzpatrick skin typing: Applications in dermatology. Indian J Dermatol Venereol Leprol 2009;75:93-6.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Díaz-Lozano M, Toussaint-Caire S, Vega-Memije ME, Mosqueda-Taylor A, Cuevas-González JC, Rodríguez-Lobato E, et al. Histopathological patterns in cheilitis of actinic prurigo. Patologia 2016;54:59-65.  Back to cited text no. 8
    
9.
Vega ME. Histopathological characteristics of actinic prurigo. Dermatol Rev Mex 1993;37:295-7.  Back to cited text no. 9
    
10.
Hua C, Zhao G, Li Y, Bie L. Minichromosome maintenance (MCM) family as potential diagnostic and prognostic tumor markers for human gliomas. BMC Cancer 2014;14:526.  Back to cited text no. 10
    
11.
Ha SA, Shin SM, Namkoong H, Lee H, Cho GW, Hur SY, et al. Cancer-associated expression of minichromosome maintenance 3 gene in several human cancers and its involvement in tumorigenesis. Clin Cancer Res 2004;10:8386-95.  Back to cited text no. 11
    
12.
Cuevas-González MV, Vega-Memije ME, Cuevas-González JC, García-Vazquez FJ, Chairez-Atienzo P, Avila-Valdez R. Expression of CD34, Ki-67, p53 and cytokeratin AE1/AE3 in solid and adenoid basal cell carcinoma. Dermatol Rev Mex 2016;60:311-8.  Back to cited text no. 12
    
13.
Cháirez-Atienzo P, Vega-Memije ME, García-Vázquez FJ, Cuevas-González JC. Expression of E-cadherin and Langerhans cells in common warts and oral papillomas. Rev ADM 2016;73:291-6.  Back to cited text no. 13
    
14.
Carreón-Burciaga RG, Mendoza-Roaf P, Amezcua-Rosas G, Bologna-Molina R, Gonzélez-Montemayor T, Gonzalez-Gonzalez R, et al. Expression of E-cadherin and syndecan-1 in lichen planus of skin and oral mucosa. Int J Odontostomatol 2014;8:439-45.  Back to cited text no. 14
    

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Correspondence Address:
María Elisa Vega-Memije
Department of Dermatology, “Dr. Manuel Gea González” General Hospital, Calzada De Tlalpan 4800, Sección XVI, Delegación Tlalpan México, D.F. C.P 14080
Mexico
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_574_17

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