Expression of p63 is the sole independent marker of aggressiveness in localised (stage I-II) Merkel cell carcinomas

Department of Biomedical Sciences and Human Oncology, University of Torino, Torino, Italy.
Modern Pathology (Impact Factor: 6.19). 07/2011; 24(11):1451-61. DOI: 10.1038/modpathol.2011.100
Source: PubMed


Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria are a matter of dispute. Specifically, no predictor is presently available in stage I-II tumours. We collected clinical and follow-up data from 70 Merkel cell carcinomas of the skin. The same cases were studied for p63 expression by immunohistochemistry, by reverse-transcription PCR (RT-PCR) and TP63 gene status by FISH and for presence of Merkel cell polyomavirus by PCR. Stage emerged as a significant prognostic parameter (P=0.008). p63 expression, detected in 61% (43/70) of cases by immunohistochemistry, was associated with both decreased overall survival (P<0.0001) and disease-free survival (P<0.0001). Variable expression patterns of the different p63 isoforms were found only in cases immunoreactive for p63. In these latter lesions, at least one of the N-terminal p63 isoforms was detected and TAp63α was the most frequently expressed isoform. TP63 gene amplification was observed by FISH in only one case. Presence of Merkel cell polyomavirus DNA sequences was detected in 86% (60/70) of Merkel cell carcinomas and did not emerge as a significant prognostic parameter. Merkel cell carcinoma cases at low stage (stage I-II) represented over half (40/70 cases, 57%) of cases, and the clinical course was uneventful in 25 of 40 cases while 15 cases died of tumour (10/40 cases) within 34 months or were alive with disease (5/40 cases) within 20 months. Interestingly, a very strict correlation was found between evolution and p63 expression (P<0.0001). The present data indicate that p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma, and in localised tumours it represents the single independent predictor of clinical evolution.

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Available from: Alberto Righi, Mar 27, 2014
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    • "For example, in the management of cutaneous melanoma, sentinel lymph node biopsy (SLNB) is now a standard of care [27]. Analogically, SLNB has gained popularity in the past years in the management of MCC, currently being recommended as standard treatment [28], independently of the size of the primary tumour [29] [30] [31] [32], as SLNB permits a pathological lymph node evaluation with less morbidity compared to elective neck dissection [33] [34]. SLNB studies have shown that about 30% of cN0 MCC patients harbour occult metastasis [35] [36], with up to 20% false negative rate [37] [38]. "
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    ABSTRACT: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy occurring mostly in older immunocompromized Caucasian males. A growing incidence of MCC has been reported in epidemiological studies. Treatment of MCC usually consists of surgical excision, pathological lymph node evaluation, and adjuvant radiotherapy. This paper reports the experience of a single tertiary center institution with 17 head and neck Merkel cell carcinoma patients. Median followup for the cohort was 37.5 months. After five years, recurrence-free survival, disease specific survival, and overall survival were 85%, 90%, and 83%, respectively. Our limited data support the use of adjuvant radiotherapy. We also report two cases of MCC located at the vestibule of the nose and two cases of spontaneous regression after diagnostic biopsy. About 40% of our patients were referred to our center for surgical revision and pathological lymph node evaluation. Increased awareness of MCC and an interdisciplinary approach are essential in the management of MCC.
    01/2013; 2013:325086. DOI:10.1155/2013/325086
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    • "Some studies have shown that p63 expression is a good prognostic marker for patients with human urothelial carcinoma [9], but is not an independent prognostic factor for overall survival of esophageal squamous cell carcinoma [10]. However, other reports have found that p63-positive cases had a worse prognosis in patients with oral squamous cell carcinoma [11], adenoid cystic carcinoma of the salivary gland [12], and Merkel cell carcinoma [13]. There are scant data on the association between p63 expression and the prognosis of MEC. "
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    ABSTRACT: Myoepithelial carcinoma is a rare tumour. The clinical and biological behaviours of these tumours are variable. Although many factors have been evaluated as potential prognostic indicators, including clinical stage, site and size of the tumour, high proliferative activity, extensive invasion into the surrounding tissue, perineural permeation, the abnormal presence of nuclear DNA content, and marked cellular pleomorphism, there are no definite histological features that clearly correlate with their behaviour. Thus, conclusions regarding prognostic factors and ideal treatment may emerge as the number of investigated myoepithelial carcinoma cases accumulate. Using immunohistochemistry, expression levels of p63 and Ki-67 were determined in 16 myoepithelial carcinoma samples and correlated with clinicopathological characteristics and patient prognosis. p63 expression was detected in six of the myoepithelial carcinoma tissues (37.5%) and Ki-67 was detected in five (31.3%). In addition, p63 and Ki-67 expression levels were associated with myoepithelial carcinoma recurrence and metastasis. All six patients with p63-positive expression died due to disease or cardiovascular disease (mean survival time = 50.5 months), and p63 expression was statistically significant with respect to survival (P = 0.01). Four patients with Ki-67-positive expression died due to disease or cardiovascular disease (mean survival time = 44.0 months); however, there was no statistically significant difference between Ki-67 expression and survival (P = 0.24). Recurrence and metastasis in myoepithelial carcinomas are more frequent in p63-positive and Ki-67-positive EMCs, and poor prognosis is associated with overexpression of p63.
    Head & Neck Oncology 03/2012; 4(1):9. DOI:10.1186/1758-3284-4-9 · 3.14 Impact Factor
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    ABSTRACT: The chromatin architectural factor DEK maps to chromosome 6p and is frequently overexpressed in several neoplasms, including small cell lung carcinoma, where it is associated with poor prognosis, tumor initiation activity and chemoresistance. DEK expression has not been studied in cutaneous Merkel cell carcinoma. We applied a DEK monoclonal antibody to 15 cases of Merkel cell carcinoma and 12 cases of small cell carcinoma. DEK nuclear immunoreactivity was scored based on percentage (0, negative; 1+, <25%; 2+, 25-50%; 3+, >50%) and intensity (weak, moderate or strong). All 15 Merkel cell carcinoma cases (100%) showed diffuse (3+) nuclear positivity (14 strong, 1 weak). Six of 12 small cell carcinoma cases (50%) showed diffuse (3+) and strong nuclear positivity, while one case exhibited focal (1+) weak nuclear positivity. The remaining five cases were negative for DEK expression. Our results suggest that DEK may be involved in the pathogenesis of Merkel cell carcinoma and therefore may provide therapeutic implications for Merkel cell carcinomas. In addition, the difference in DEK expression between Merkel cell carcinoma and small cell carcinoma suggests possible separate tumorigenesis pathways for the two tumors.
    Journal of Cutaneous Pathology 07/2012; 39(8):753-7. DOI:10.1111/j.1600-0560.2012.01941.x · 1.58 Impact Factor
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