DermatopathologyD2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: A marker of metastatic risk
Section snippets
Patients
Six tertiary care hospitals of Spain participated in this study. Records at these centers were searched to identify patients who had developed MSCCs between 2001 and 2010. Fifty patients with 51 primary MSCCs that had evolved to histologically confirmed lymph node (n = 46) or cutaneous in-transit (n = 5) metastases were included in the study. A control group of 50 patients with cSCCs who had not developed any metastasis (non-MSCCs) in a 5-year follow-up period was also evaluated. All the tumors
Lymphatic metastases status and clinicopathological features
The clinicopathological features of the patients and tumors are detailed in Table I. The mean follow-up period of time in the MSCC group was 24 months. The mean period of time between the diagnosis of the primary MSCCs and their lymphatic metastases was 7.2 months (n = 44). Four of the 101 (3.9%) cSCCs in the study showed angiolymphatic invasion on basis of the hematoxylin-eosin staining.
No differences regarding gender, age, sun-exposed area, or immunosuppression status were observed between
Discussion
There is a lack of reliable prognostic markers in cSCC. It would be of special interest to identify aggressive tumors that require additional treatments such as lymphadenectomy or radiation therapy. We have evaluated the use of podoplanin expression as a prognostic marker in cSCC.
Lymphatic invasion is rarely seen in primary cSCC by routine histology probably because of obliteration and solid tumor emboli that make it imperceptible. We have shown that D2-40 positivity in endothelial cells helps
References (48)
- et al.
A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumor (T) characteristics
J Am Acad Dermatol
(2011) - et al.
Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study
Lancet Oncol
(2008) - et al.
Lateral peritumoral lymphatic vessel invasion can predict lymph node metastasis in esophageal squamous cell carcinoma
Mod Pathol
(2007) - et al.
Clinico-pathological factors influencing postoperative prognosis in patients with small-sized adenocarcinoma of the lung
J Thorac Cardiovasc Surg
(2008) - et al.
Intratumoral lymphatics and lymphatic invasion are associated with tumor aggressiveness and poor prognosis in renal cell carcinoma
Urology
(2008) - et al.
Lymphatic invasion detected by D2-40/S-100 dual immunohistochemistry does not predict sentinel lymph node status in melanoma
J Am Acad Dermatol
(2009) - et al.
D2-40 lymphatic marker for detecting lymphatic invasion in thin to intermediate thickness melanomas: association with sentinel lymph node status and prognostic value–a retrospective case study
J Am Acad Dermatol
(2011) - et al.
Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors
Am J Pathol
(2005) - et al.
D2-40 immunoreactivity in penile squamous cell carcinoma: a marker of aggressiveness
Hum Pathol
(2011) - et al.
The transmembrane domain of podoplanin is required for its association with lipid rafts and the induction of epithelial-mesenchymal transition
Int J Biochem Cell Biol
(2011)
Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton
Cancer Cell
Low D2-40 immunoreactivity correlates with lymphatic invasion and nodal metastasis in early-stage squamous cell carcinoma of the uterine cervix
Mod Pathol
Front pattern of invasion in squamous cell carcinoma of the penis: new prognostic factor for predicting risk of lymph node metastases
Urology
Prognostic factors in squamous cell carcinoma of the lower lip
Hum Pathol
Prognostic significance of peritumoral lymphatic vessel density and vascular endothelial growth factor receptor 3 in invasive squamous cell cervical cancer
Transl Oncol
Cancer invasion and the microenvironment: plasticity and reciprocity
Cell
The mysteries of geographic variability in nonmelanoma skin cancer incidence
Arch Dermatol
Cutaneous squamous-cell carcinoma
N Engl J Med
In-transit metastasis from primary cutaneous squamous cell carcinoma in organ transplant recipients and nonimmunosuppressed patients: clinical characteristics, management, and outcome in a series of 21 patients
Dermatol Surg
Histopathological characteristics of metastasizing squamous cell carcinoma of the skin and lips
Histopathology
Detection of lymphatic invasion in early stage primary colorectal cancer with the monoclonal antibody D2-40
Eur Surg Res
Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences
Am J Surg Pathol
Invasive lobular carcinoma of the breast: role of endothelial lymphatic marker D2-40
Ann Clin Lab Sci
Cited by (26)
Differential Molecular Expression Patterns Associated with Metastasis in Cutaneous Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
2021, Journal of Investigative DermatologyCitation Excerpt :Preserved expression of membranous E-cadherins in invasive or metastatic disease supports the theory of collective cancer invasion in cSCC, whereby adjoining cells maintain their connections in the process of tumor migration; conversely, loss of membranous but increased cytoplasmic E-cadherin suggests EMT as the driving force, whereby malignant epithelial cells transform phenotype to that of mesenchyme that more easily invades tissues. Combined results of two included studies showed no difference in the pattern of E-cadherin expression between metastatic and nonmetastatic primary cSCCs with both groups showing a loss of membranous protein and moderate cytoplasmic expression (Toll et al., 2012; Vinicius et al., 2011). One study included in this analysis also reported an upregulation of E-cadherin transcription repressors involved in EMT (Twist, Zeb1) and markers of EMT (vimentin) in tumors that metastasized (Toll et al., 2012).
A review of terms used to define cutaneous squamous cell carcinoma with a poor prognosis
2020, Actas Dermo-SifiliograficasMetastatic Cutaneous Squamous Cell Carcinomas
2017, Introduction to Cancer MetastasisMultivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck
2016, Journal of the American Academy of DermatologyEpithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases
2013, Journal of Dermatological ScienceCitation Excerpt :Another protein associated to the mesenchymal phenotype is Podoplanin, a transmembrane mucin important in mediating cellular contractile properties and cytoskeletal reorganization [5,14,15]. Podoplanin expression is increased in metastatic cSCCs (MSCC) [16–18]. We have studied the immunohistochemical expression of several EMT markers in metastatic cSCCs and their corresponding metastases.
Multiple Bowen Disease Lesions with the "eyeliner Sign" in a Psoriasis Patient after Long-Term Narrow-Band Ultraviolet B Light Therapy
2024, American Journal of Dermatopathology
Supported in part by grants PI041728, PI10/00785, and RD09/0076/00036 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad, Federación Española de Enfermedades Raras (FEDER), Spain, and the Xarxa de Bancs de tumors sponsored by Pla Director d'Oncologia de Catalunya.
Conflicts of interest: None declared.