The Stem Cell-associated Transcription Factor SOX2 as a Diagnostic Marker of High-grade Squamous Intraepithelial Lesion of the Uterine Cervix in Comparison With p16 and Ki-67

In patients with high-grade squamous intraepithelial lesion (HSIL) of the vulva, the presence of multiple lesions, called multifocal HSIL, is common. The aim of this exploratory study was to investigate biomarker expression profiles in multifocal HSIL. In total, 27 lesions from 12 patients with high-risk human papillomavirus (HPV)-positive multifocal HSIL were tested for HPV genotype, expression of p16INK4a and Ki-67, and DNA methylation of six genes. HPV16 was found most commonly in 21 (77.8%) HSILs. In two (16.4%) patients, HPV genotype differed between the lesions. All lesions demonstrated diffuse p16INK4a staining, of which three (11.1%) were combined with patchy staining. One patient (8.3%) demonstrated markedly different DNA methylation levels between lesions. Generally, heterogeneity in methylation profiles was observed between different patients, even when other biomarkers showed similar expression. In conclusion, this study is the first to demonstrate heterogeneity of individual lesions in patients with multifocal HSIL. The studied biomarkers have the potential to refine prognostic and predictive diagnostics. Future prospective, longitudinal studies are needed to further explore the potential of a biomarker profile for management of patients with multifocal HSIL.

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The utility of p16INK4aand Ki-67 to identify high-grade squamous intraepithelial lesion in adolescents and young women

Indian Journal of Pathology and Microbiology ◽

10.4103/0377-4929.101740 ◽

2012 ◽

Vol 55 (3) ◽

pp. 339 ◽

Cited By ~ 3

Author(s):

José Eleutério ◽

DianeM Cavalcante ◽

IaraM Linhares ◽

MargaridaM.L Pompeu ◽

PauloC Giraldo

Keyword(s):

Young Women ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Ki 67 ◽

Intraepithelial Lesion

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Adenoid Cystic Carcinoma of the Uterine Cervix: A Report of 2 Cases

Case Reports in Pathology ◽

10.1155/2017/8401741 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4

Author(s):

Meryem Rais ◽

Jinane Kharmoum ◽

Soumaya Ech-Charif ◽

Basma El Khannoussi

Keyword(s):

Adenoid Cystic Carcinoma ◽

Uterine Cervix ◽

Clinical Course ◽

Invasive Squamous Cell Carcinoma ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Pathological Characteristics ◽

Adenoid Cystic ◽

Intraepithelial Lesion ◽

Aggressive Clinical Course

Adenoid cystic carcinoma is malignant tumor that exceptionally occurs in the uterine cervix. It is mostly seen in postmenopausal women and has an aggressive clinical course. We report two cases of an adenoid cystic carcinoma associated with a high grade squamous intraepithelial lesion and invasive squamous cell carcinoma of the uterine cervix and discuss briefly its clinical and pathological characteristics.

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Comparative Evaluation of SOX2 and p16 Expression in Intraepithelial Neoplasia and Invasive Cancer of Cervix

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/50358.15426 ◽

2021 ◽

Author(s):

Sowmya Dayalan ◽

Vijayashree Raghavan

Keyword(s):

Transcription Factor ◽

Invasive Cancer ◽

P Value ◽

Low Grade ◽

High Grade ◽

Diagnostic Biomarker ◽

Squamous Intraepithelial Lesion ◽

Chi Square ◽

Intraepithelial Lesion ◽

P16 Expression

Introduction: SRY (Sex determining region Y)-Box Transcription Factor 2 (SOX2), a transcription factor functioning as a stem cell marker has been studied in many cancers for its role as an oncogene. This study evaluates the expression of SOX2 and protein 16 (p16) expression in cervical with the intent to establish their role as a diagnostic biomarker. Aim: To evaluate the nature of SOX2 expression in cervical cancer and in intraepithelial lesions of cervix and compare it with the expression of p16 with the intent to establish its role as a diagnostic biomarker. Materials and Methods: This study was a retrospective observational study conducted in the Department of Pathology, Chettinad Hospital and Research Institute, Chennai, Tamil Nadu, India from October 2018 to September 2019. Archival blocks for study were collected from cases between January 2012 to December 2017. Immunohistochemistry for SOX2 and p16 on 61 cases of cervical lesions including SCC, Low-grade Squamous Intraepithelial Lesion (LSIL), High-grade Squamous Intraepithelial Lesion (HSIL) and normal cervix were done. A chi-square analysis was used to determine the relationship of SOX2 and p16 expression in different lesions and compared the same. All collected data was tabulated and analysed by Statistical Package for Social Sciences (SPSS) version 23.0 and was compared by chi-square tests. Results: In the total 61 cases (majority with LSIL, n=21, 34.43%, SCC were 19 (31.15%), HSIL were 20 (32.79%) and adenosquamous carcinoma were 1 (1.64%), SOX2 (p-value <0.001) and p16 (p-value 0.0016) showed over-expression in SCC and HSIL with significant p-value, LSIL showed low expression. SOX2 and p16 expression was limited to the basal one-third in LSIL cases, whereas it was expressed up to two-third or full thickness in HSIL cases. Also, SOX2 and p16 had a significant relationship with p-value=0.001. SOX2 was sensitive for SCC with 84.21% sensitivity and p16 was sensitive for HSIL with 90% sensitivity. Conclusion: Both SOX2 and p16 show increasing expression as the lesion progresses from low grade dysplasia to high grade dysplasia and invasive cancer and can complement each other to make a definitive diagnosis.

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Clinicopathological Characteristics of Pleomorphic High-Grade Squamous Intraepithelial Lesion of the Uterine Cervix: A Single-Institutional Series of 31 Cases

Diagnostics ◽

10.3390/diagnostics10080595 ◽

2020 ◽

Vol 10 (8) ◽

pp. 595

Author(s):

Hyunjin Kim ◽

Sangjoon Choi ◽

Sung-Im Do ◽

Sang Hwa Lee ◽

Nara Yoon ◽

...

Keyword(s):

Uterine Cervix ◽

Clinicopathological Characteristics ◽

Surface Epithelium ◽

Invasive Squamous Cell Carcinoma ◽

High Grade ◽

Ki 67 ◽

Nuclear Atypia ◽

Intraepithelial Lesion ◽

Intraepithelial Lesions ◽

Nuclear Enlargement

We investigated the clinicopathological characteristics of 31 cases of pleomorphic high-grade squamous intraepithelial lesions (PHSIL) of the uterine cervix. We reviewed electronic medical records and all available slides to collect clinical and pathological information. PHSILs were histologically characterized by significant nuclear enlargement, marked pleomorphism, hyperchromasia, increased mitotic activity, and frequent atypical mitoses. In the majority of cases (24/31; 77.4%), this striking nuclear atypia involved both the surface epithelium and the endocervical glands. In the remaining seven cases, pleomorphic cells were observed in the surface epithelium only. PHSILs involving both the surface epithelium and glands showed higher mitotic counts and Ki-67 labelling indices than the surface-only PHSILs. Invasive squamous cell carcinoma was present in only one case (3.2%), and none developed recurrent disease. Our observations of striking nuclear atypia in cases of HSIL did not indicate increased aggressiveness. Further investigations are required for confirmation of our data in larger cohorts.

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p16 and Ki-67 Immunostaining in Atypical Immature Squamous Metaplasia of the Uterine Cervix: Correlation With Human Papillomavirus Detection

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-1343-pakiia ◽

2007 ◽

Vol 131 (9) ◽

pp. 1343-1349 ◽

Cited By ~ 7

Author(s):

Lori Iaconis ◽

Elizabeth Hyjek ◽

Lora H. Ellenson ◽

Edyta C. Pirog

Keyword(s):

Polymerase Chain Reaction ◽

Squamous Metaplasia ◽

Human Papillomaviruses ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Chain Reaction ◽

Ki 67 ◽

Intraepithelial Lesion ◽

Polymerase Chain ◽

Cervical Mucosa

Abstract Context.—Atypical immature squamous metaplasia (AIM) of the cervix is a loosely defined entity characterized by immature metaplastic cells with mild cytologic atypia. Objective.—To examine whether a combination of immunostaining for p16 and Ki-67 could be used to stratify AIM cases into 3 categories: benign, cases with nondiagnostic atypia, and high-grade squamous intraepithelial lesion (HSIL). Design.—The study consisted of 37 cases of AIM, 23 cases of benign cervical mucosa (NEG), and 36 cases of HSIL. All cases were tested for high-risk human papillomaviruses using SPF 10 polymerase chain reaction and immunostained for p16 and Ki-67. Results.—All cases of HSIL were positive for both p16 and Ki-67. All but 2 benign control cases were negative for both p16 and Ki-67. Seven cases of AIM (19%) displayed a pattern of immunostaining identical to HSIL, and these most likely represent a spectrum of HSIL. A total of 54% of cases of AIM were negative for both p16 and Ki-67, consistent with benign reactive atypia. Two AIM cases (5%) were negative for p16 and positive for Ki-67 in the area adjacent to an ulcer, representing regeneration. Finally, 22% of AIM cases were positive for p16 and negative for Ki-67; such cases may represent a precursor of HSIL or, alternatively, a regressing HSIL. Conclusion.—The combination of immunostaining for p16 and Ki-67 is helpful in limiting of the number of cases with nondiagnostic atypia of the cervix.

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