Cell kinetic markers in cutaneous squamous and basal cell carcinoma of the head and neck / Marcadores cinéticos celulares em carcinomas espinocelulares e basocelulares cutâneos de cabeça e pescoço

Abstract Introduction: Proliferation markers play a significant role in the biologic behavior of tumors. Geminin is a known inhibitor of the cell cycle and DNA replication and has not been previously reported in cutaneous basal and squamous cell carcinomas of the head and neck. Objectives: We aimed to investigate proliferation markers ki67, MCM2, and geminin in head and neck cutaneous basal and squamous cell carcinomas. Methods: Forty cases of each tumor were immuostained with ki67, MCM2, and geminin followed by assessment of labeling indices (LIs). MCM2/ki67- and geminin/ki67-ratios were also determined; t-test was used for statistical analysis (p<0.05). Results: There was no significant difference in ki67 (p = 0.06) and MCM2 (p = 0.46) between cutaneous basal and squamous cell carcinomas; however, geminin LI was significantly higher in squamous cell carcinomas compared to cutaneous basal cell carcinomas (p < 0.001). Only geminin/ki67 showed a significant difference between the two tumors with the ratio showing significantly higher numbers in squamous cell carcinomas (p = 0.015). Conclusions: Geminin could be regarded as an effective factor in the pathogenesis of head and neck cutaneous cutaneous basal cell carcinomas and squamous cell carcinomas and may be one of the responsible elements in the difference between the biologic behavior of these tumors. © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Resumo Introdução: Marcadores de proliferação têm um papel significativo no comportamento biológico dos tumores. A geminina é um inibidor conhecido do ciclo celular e da replicação do DNA e não foi relatada anteriormente em carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço. Objetivo: Investigar os marcadores de proliferação ki67, MCM2 e geminina em carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço. Método: Foram submetidos 40a casos de cada tumor à imunocoloração com ki67, MCM2 e geminina, seguida pela avaliação do índice de marcação.Também foram determinadas as razões MCM2/ki67 e geminina/ki67 e o teste t foi usado na análise estatística (p < 0,05). Resultados: Não houve diferença significativa no ki67 (p = 0,06) e no MCM2 (p = 0,46) entre carcinomas basocelulares e espinocelulares; no entanto, o índice de marcação da geminina foi significativamente maior no carcinomas espinocelulares em comparação ao carcinomas basocelulares (p < 0,001). Somente a razão geminina/ki67 mostrou diferença significativa entre os dois tumores, a razão mostrou números significativamente mais altos nos carcinomas espinocelulares (p = 0,015). Conclusões: A geminina pode ser considerada um fator efetivo na patogênese dos carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço e pode ser um dos elementos responsáveis pela diferença entre o comportamento biológico desses tumores.

Complejo mcm2-7. Revisión bibliográfica / MCM2-7 complex: a review

La formación de nuevas células se genera a partir de células preexistentes a través de una serie ordenada de eventos denominada ciclo celular. El control de este es fundamental para la integridad del genoma, por lo que hay múltiples proteínas regulando este proceso. Actualmente, se conoce que el complejo MCM2-7 tiene un rol esencial en la replicación del ADN, específicamente involucrado en la proliferación, durante el ciclo celular. La identificación inmunohistoquimica de las proteínas de este complejo a nivel tisular, podría ser una herramienta muy útil, para usarlos como biomarcadores y así comprender uno de los mecanismos biológicos que se ven afectados en el cáncer. Nuestro objetivo es realizar una revisión del complejo MCM2-7, ya que estas proteínas como se ha descrito, podrían comportarse como buenos marcadores biológicos de proliferación celular, y así poder realizar un buen diagnóstico, pronóstico y futuros blancos terapéuticos de aquellas lesiones principalmente neoplásicas , principalmente las que asientan a nivel de la mucosa bucal.

New cells are formed from preexisting cells through an ordered series of events called cell cycle. As the control of this cycle is fundamental for genome integrity, multiple proteins regulate this process. We currently know that the MCM2-7 complex has a major role in DNA replication in the cell cycle, in particular regarding proliferation. The immunohistochemical identification of the proteins in this complex on tissues may be useful, as they could be used as biomarkers and would help us understand one of the biological mechanisms affected in cancer processes. Our aim is to collect the existing evidence regarding the members of the MCM2-7 complex, since these proteins could be effective biological cell proliferation markers, which would help practitioners make accurate diagnosis, prognosis and future therapeutic targets of lesions that are mainly neoplastic, especially in the oral mucosa.

Diagnostic value of p16/mcm2 dual staining in cervical intraepithelial neoplasia and its association with high-risk HPV infection / 中华流行病学杂志

Objective To study the expression of p16/mcm2 immunocytochemical dual staining in cervical lesions and its association with high-risk HPV infection,and discuss its clinical value in cervical cancer screening.Methods From May to December 2015,a total of 1 127 women receiving cervical cancer screening,high-risk HPV (HR-HPV) test and liquid-based cytology test were included in the study.p16/mcm2 immunocytochemical dual staining was performed on residual cytology specimens and the results were compared with histopathology results.Results p16/mcm2 had a higher expression risk in HPV16/18 group and other HR-HPV group compared with HPV negative group,with OR of 15.95 (95％CI:9.59-26.51) and 10.53 (95％CI:7.41-14.98),respectively.The positive rate of p16/mcm2 increased with cervical intraepithelial neoplasia (CIN) severity,and was higher in both CIN2 group and CIN3 group than in benign lesion group (P＜0.05).The overall sensitivity of p16/mcm2 to detect CIN2 + and CIN3 + lesions were 86.1％ and 92.0％,respectively,and the overall specificity were 46.1％ and 44.4％,respectively.In group with cytologic diagnoses of atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL),the sensitivity to detect CIN2 + and CIN3 + lesions were 85.7％ and 87.5％,respectively,and the specificity were 45.5％ and 44.1％,respectively.Conclusions p16/mcm2 dual staining has higher sensitivity than cytology test and better specificity than HPV test.It can identify high-grade cervical lesions and guide the classification of CIN.p16/mcm2 might be used as an innovative biomarker for cervical cancer screening.

Diagnostic value of p16/mcm2 dual staining in cervical intraepithelial neoplasia and its association with high-risk HPV infection / 中华流行病学杂志

Objective To study the expression of p16/mcm2 immunocytochemical dual staining in cervical lesions and its association with high-risk HPV infection,and discuss its clinical value in cervical cancer screening.Methods From May to December 2015,a total of 1 127 women receiving cervical cancer screening,high-risk HPV (HR-HPV) test and liquid-based cytology test were included in the study.p16/mcm2 immunocytochemical dual staining was performed on residual cytology specimens and the results were compared with histopathology results.Results p16/mcm2 had a higher expression risk in HPV16/18 group and other HR-HPV group compared with HPV negative group,with OR of 15.95 (95％CI:9.59-26.51) and 10.53 (95％CI:7.41-14.98),respectively.The positive rate of p16/mcm2 increased with cervical intraepithelial neoplasia (CIN) severity,and was higher in both CIN2 group and CIN3 group than in benign lesion group (P＜0.05).The overall sensitivity of p16/mcm2 to detect CIN2 + and CIN3 + lesions were 86.1％ and 92.0％,respectively,and the overall specificity were 46.1％ and 44.4％,respectively.In group with cytologic diagnoses of atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL),the sensitivity to detect CIN2 + and CIN3 + lesions were 85.7％ and 87.5％,respectively,and the specificity were 45.5％ and 44.1％,respectively.Conclusions p16/mcm2 dual staining has higher sensitivity than cytology test and better specificity than HPV test.It can identify high-grade cervical lesions and guide the classification of CIN.p16/mcm2 might be used as an innovative biomarker for cervical cancer screening.

Comparison of proliferative activity of epithelial cells between the follicles of impacted teeth / Comparación de la actividad proliferativa de las células epiteliales entre los folículos de dientes impactados

The aim of this comparative observational study was to compare the proliferative activity of dental follicles surrounding impacted maxillary canines and mandibular third molars. Following extraction, forty follicles of the impacted mandibular third molars and 40 follicles of the impacted maxillary canines were removed. Epithelial cell proliferative activity of these samples was assessed using immunohistochemical labeling for Ki-67, minichromosome maintenance 2 (MCM-2) protein and epithelial growth factor receptor (EGFR). Intensity and extent of Ki-67, MCM-2 and EGFR expressions were evaluated by a scoring formula. The lining epithelium of the maxillary canine follicles had mean scores of 4.65±0.27 for Ki-67, 1.25±0.33 for MCM-2 and 7.30±0.23 for EGFR which were not significantly different than those expressed in the mandibular third molar follicles (4.46±0.26 for Ki-67, 1.39±0.33 for MCM-2 and 7.21±0.20 for EGFR). The expression of Ki-67 and MCM-2 could not be detected in the epithelial remnants within the connective tissue in both groups. EGFR expression, detected in the epithelial remnants in both groups, was not significantly different (7.28±0.14 in the canine group as opposed to 7.21±0.16 in the third molar group). Based on these findings, it can be deduced that impacted mandibular third molars and maxillary canines carry similar risk of pathology development.

El objetivo fue comparar la actividad proliferativa de los folículos dentarios que rodean a dientes caninos maxilares y terceros molares mandibulares impactados. Luego de realizada la extracción dentaria, se removieron 40 folículos dentarios de los terceros molares mandibulares impactados y 40 de caninos maxilares impactados. Se evaluó la actividad proliferativa de las células epiteliales de estas muestras mediante marcaje inmunohistoquímico para Ki-67, para la proteína de mantenimiento minicromosoma 2 (MCM-2) y para el receptor del factor de crecimiento epitelial (EGFR). Se evaluó la intensidad y extensión de Ki-67, MCM-2 y las expresiones de EGFR mediante una fórmula de puntuación. El epitelio de revestimiento de los folículos correspondientes a los caninos maxilares presentaron valores promedios de 4,65±0,27 para Ki-67, 1,25±0,33 para MCM-2 y 7,30±0,23 para EGFR, que no fueron significativamente diferentes de los expresados en los folículos de terceros molares mandibulares (4,46±0,26 para Ki-67, 1,39±0,33 para MCM-2 y 7,21±0,20 para EGFR). La expresión de Ki-67 y MCM-2 no pudo ser detectada en los restos epiteliales dentro del tejido conectivo en ambos grupos. La expresión de EGFR, detectada en los restos epiteliales en ambos grupos, no fue significativamente diferente (7,28±0,14 en el grupo de los caninos, y 7,21±0,16 en el grupo de los terceros molares). Sobre la base de estos resultados, se puede deducir que la retención de terceros molares y caninos maxilares conlleva un riesgo similar para el desarrollo de patología.

Expression of MCM2 and its prognostic significance in patients with non-small cell lung cancer / 肿瘤研究与临床

Objective To investigate the expression of MCM2 and its prognostic significance in non-small cell lung cancer (NSCLC). Methods The expression of MCM2 was measured by immunohistochemistry in 73 cases of NSCLC and 10 cases of normal lung tissue. The correlations between the expression of MCM2 and clinic-opathological parameters and prognosis were investigated. Results There was no MCM2 expression in normal lung tissue and positive rate of MCM2 expression was 87.7% in NSCLC. The difference between the two groups was significant (P<0.001). The expression of MCM2 in poorly differentiated NSCLC patients was significantly higher than that in moderately- and well-differentiated NSCLC patients (P=0.008). The expression of MCM2 in patients with squamous carcinoma was higher than that in patients with adenocarcinoma (P=0.005). The hazard ratio was significantly higher(RR=3.389, 95 % CI=1.803-7.146,P<0.001), and the accumulated survival rate was significantly lower (P=0.001) in NSCLC patients with higher MCM2 expression than that of lower expression. MCM2 was independent prognostic factor of NSCLC patients (P=0.041). Conclusion MCM2 could reflect the reproductive activity of NSCLC and has some clinical significance for assessing the development and prognosis of NSCLC. MCM2 was a potential target for future treatment.

Expression of the minichromosome maintenance 2 protein and the cell surface molecule CD24 and their prognostic significance in patients with non-small cell lung cancer / 中华全科医师杂志

Objective To explore expression of the minichromosome maintenance 2 (MCM2)protein and the mucin-like cell surface adhesion molecule CD24 in non-small cell lung cancer (NSCLC) and their relationship with its prognosis. Methods Seventy-three patients of NSCLC diagnosed for the first time and received surgical treatment in Xuanwu Hospital, Beijing were selected for the study. Expression of the MCM2 and CD24 in pathological specimens of the patients was measured by immunohistochemistry and their relationship with its prognosis was analyzed retrospectively. Results High-level expression of the MCM2 and CD24 was seen in 42 and 54 of 73 NSCLC patients, accounting for 57. 5 percent and 74. 0 percent,respectively. Risk of death for the patients with high-level expression of the MCM2 or the CD4 was significantly higher as compared to those with low-level expression ( P ＜ 0. 05 ). Risk of death for patients with both high-level expression of the MCM2 and CD24 was significantly higher than that in those with only high-level expression of the MCM2 or the CD24 (HR =2. 59, 95%CI 1.40 -4. 80, P=0. 002) and in those with both low-level expression of them ( HR = 15.32, 95 % CI = 2.07 - 113.41, P = 0. 008 ). But there was no significant difference in risk of death between patients with high-level expression of the MCM2 or CD24 and those with low-level expression of both of them ( HR = 5. 60, 95% CI 0. 79 - 44. 82, P = 0. 083 ), and cumulative survival rate of patients with both high-level expression of the MCM2 and CD24 was significantly lower than those with only high-level expression of the MCM2 or the CD24 ( P = 0. 001 ). Conclusions Both expression of the MCM2 and the CD24 are independent prognostic factors for NSCLC and combined detection of the two markers have higher prognostic value for it.

Expression of minichromosome maintenance 2 protein in normal skin as well as lesions of malignant hyperplasia and non-malignant hyperplasia / 中华皮肤科杂志

Objective To detect the expression intensity and distribution of minichromosome mainte-nance 2 protein (MCM-2) in normal skin and lesions of malignant and non-malignant hyperplasia. Methods Three groups of samples were collected, I.e., malignant group (including 15 cases of Bowen disease or highly differentiated squamous cell carcinoma of Grade Ⅰ or Ⅱ ), non-malignant group (including 4 cases of chro-momycosis, 2 cases of sporotrichosis, 5 cases of seborrheic keratosis, 4 cases of verruca vuigaris, 4 cases of chronic eczema, 4 cases of cutaneous fibroma), and normal group (10 cases of normal human control). The distribution and intensity of MCM-2 expression in the epidermis of these samples were assessed by immuno-histochemical SP method. Results The expression of MCM-2 was observed in basal and superbasal layer of epidermis in lesions of malignant and non-malignant hyperplasia, and only in epidermal basal layer in normal skin. A significant increment was observed in the density of MCM-2 positive cells in superbasal layer in malignant lesion compared with the non-malignant lesion. The epidermal expression level of MCM-2 in the non-malignant lesion was significantly lower than that in the malignant lesion, but higher than that in the normal skin (μ = -2.529, -3.705, respectively, both P < 0.05); the same was true for the proportion of MCM-2-postive basal cells. Conclusions The expression of MCM-2 protein varies with the proliferation status of epidermal cells, and may serve as an objective marker for epidermal cell proliferation.

The research on expression and clinical significance of MCM2 in BTCC / 中国癌症杂志

Background and purpose:It is verifi ed that MCM2 is a specifi c marker in the cell cycle,and expressed in all cells entering into the cycle,however,no expression is found in the differentiated cells and static period cell.Therefore,in the abnormally proliferative developmental cells and mutagenic cells,MCM2 could be used to mark the status of the cells as a cellular proliferative marker,and then to be a diagnostic tool for some heterotypical pathological changes and tumors.Our study demonstrated that the expression and clinical significance of MCM2 in bladder transitional cell cancer(BTCC).Methods:The expression of MCM2 was examined by immunohistochemistry Streptavidin-Peroxidase method in 12 cases of normal bladder tissues and 42 cases of BTCC.Results:The positive expression of MCM2 in BTCC was 100%,whereas in normal tissues,no positive expression was found(P0.05).The expression of MCM2 was closely associated with tumor pathological grade(P

Expression and clinical significance of Rb gene and MCM2 in prostate cancer / 重庆医科大学学报

Objective: To study the expression of retinoblastoma susceptibility gene(Rb) and minichromosome maintenance protein 2(MCM2) in primary prostate cancer(PCa) and its clinical significance.Methods: The expression of MCM2 protein and pRb were detected in 49 cases of PCa,20 cases of benign prostate hyperplasia(BPH),10 cases of normal prostate tissues(NP) by EliVisionTM plus immunohistochemical staining.Results: The positive expression rate of pRb in PCa,BPH,NP were 44.90%,80% and 90% respectively.The expression level of pRb in PCa was significantly lower than that in BPH(P