Local and regional recurrence of vulval cancer: management dilemmas

Coulter, J. B. S.; Gleeson, Noreen

doi:10.1016/s1521-6934(03)00050-6

Cited by 65 publications

(56 citation statements)

References 47 publications

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“…As observed in this study, low levels of PLXDC2, concomitant with high expression of GNB3, mitigate lymph node metastasis, which is the major prognostic factor of VSCC (28). This association correlates with a better prognosis, because it is related to earlystage tumors (FIGO I and II) and higher DFS rates.…”

Section: Discussionsupporting

confidence: 69%

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

Lavorato-Rocha

Akagi

Maia

et al. 2016

Molecular Cancer Research

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Vulvar squamous cell carcinoma (VSCC) is a rare disease that has a high mortality rate ($40%). However, little is known about its molecular signature. Therefore, an integrated genomics approach, based on comparative genome hybridization (aCGH) and genome-wide expression (GWE) array, was performed to identify driver genes in VSCC. To achieve that, DNA and RNA were extracted from frozen VSCC clinical specimens and examined by aCGH and GWE array, respectively. On the basis of the integration of data using the CONEXIC algorithm, PLXDC2 and GNB3 were validated by RT-qPCR. The expression of these genes was then analyzed by IHC in a large set of formalin-fixed paraffin-embedded specimens. These analyses identified 47 putative drivers, 46 of which were characterized by copy number gains that were concomitant with overexpression and one with a copy number loss and downregulation. Two of these genes, PLXDC2 and GNB3, were selected for further validation: PLXDC2 was downregulated and GNB3 was overexpressed compared with non-neoplastic tissue. By IHC, both proteins were ubiquitously expressed throughout vulvar tissue. High expression of GNB3 and low PLXDC2 immunostaining in the same sample was significantly associated with less lymph node metastasis and greater disease-free survival. On the basis of a robust methodology never used before for VSCC evaluation, two novel prognostic markers in vulvar cancer are identified: one with favorable prognosis (GNB3) and the other with unfavorable prognosis (PLXDC2).Implications: This genomics study reveals markers that associate with prognosis and may provide guidance for better treatment in vulvar cancer.

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Section: Discussionsupporting

confidence: 69%

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

Lavorato-Rocha

Akagi

Maia

et al. 2016

Molecular Cancer Research

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“…This figure is a bit higher than that reported by Coulter and Gleason [29], who found a recurrence rate of about one third. Their study showed that the size of the lesion, close margins of resection (<1 cm) and lymph node status at primary surgery were the main predictors of recurrence [29]. We found local recurrence in 47% of our patients; the literature figures for this complication range from 53 to 86% [28,29,30,32,33].…”

Section: Discussioncontrasting

confidence: 62%

“…Surgery is the most common treatment for vulvar carcinoma [28,29], and many different types of procedures have been advocated over the course of time [13,28,30,31]. Current FIGO recommendations state that in situ (FIGO stage 0) and FIGO stage IA (≤2 cm) tumors may be treated by superficial partial vulvectomy, FIGO stages IB (stromal invasion >1.0) and II (>2 cm) may be treated with partial vulvectomy and lymphadenectomy, and FIGO stage III (any size with adjacent spread) and IVA (tumor invasion to other organs) may be treated with radical (or en bloc) vulvectomy and lymphadenectomy [30,32].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Sociodemographic and Clinicopathological Features in Brazilian Patients with Vulvar Squamous Cell Carcinoma

Maia

Cestari

Lavorato-Rocha

et al. 2012

Gynecol Obstet Invest

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Aim: To investigate sociodemographic and clinical-epidemiological profiles of patients with vulvar carcinoma in São Paulo, the largest city of Brazil, to establish a more consistent profile of these features once the incidence of vulvar carcinoma has risen considerably. Data regarding the epidemiological aspects of this tumor are scarce. Methods: A retrospective study was performed using 300 medical records from patients diagnosed with squamous cell carcinoma of the vulva and surgically treated at A.C. Camargo Hospital in São Paulo, Brazil, from 1978 to 2009. Results: The median age of onset was 70 years, ranging from 15 to 98 years, and most women were white (88.51%). Most patients (83.54%) had little or no schooling and had the lowest survival curve. Many patients were diagnosed in the early stages of the disease (57.09% FIGO IB), 59% had complications due to surgery and 43.71% had disease recurrence, of which about 70% died. Conclusions: Our study adds 300 Brazilian cases of vulvar carcinoma to the world literature. Given the high rate of disease recurrence and mortality in Brazil, we conclude that regular gynecologic evaluation and educational policies should be reinforced in order to raise awareness for vulvar cancer.

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“…Vulvar carcinoma is a rare genital cancer counting for 3‐5% of all gynecological carcinomas and with an incidence ranging from 1 to 2 per 100 000 person‐years worldwide 1, 2. In Norway, the overall incidence of VSCC has increased from 1.70 to 4.66 per 100 000 person‐years in past 50 years 3.…”

Section: Introductionmentioning

confidence: 99%

“…In Norway, the overall incidence of VSCC has increased from 1.70 to 4.66 per 100 000 person‐years in past 50 years 3. Radical surgery has been the standard treatment for most patients but is accompanied by physical and psychological adverse effects and a considerable morbidity 1, 4. Less radical treatments have been introduced in the last two decades, yet with no significant improvements in survival 5.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of CHK1 activation in vulvar squamous cell carcinoma and its potential as a therapeutic target in vitro

et al. 2018

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CHK1 is an important regulator of the cell cycle and DNA damage response, and its altered expression has been identified in various tumors. Chk1 inhibitors are currently being evaluated as monotherapy and as potentiators of chemotherapy in clinical settings. However, to our knowledge, no previous study has investigated either the activation status or the therapeutic potential of CHK1 targeting in vulvar cancer. Therefore, we examined the expression status of activated CHK1 forms pCHK1Ser345, pCHK1Ser317, pCHK1Ser296, and pCHK1Ser280 in 294 vulvar squamous cell carcinomas (VSCC) using immunohistochemistry and analyzed their relationships with various clinicopathological variables and clinical outcome. To aid translation of preclinical studies, we also assessed cell sensitivity to the Chk1 inhibition in two vulvar cancer cell lines. Compared to the levels of pCHK1Ser345, pCHK1Ser317, pCHK1Ser296, and pCHK1Ser280 in normal vulvar squamous epithelium, high nuclear pCHK1Ser345 expression was found in 57% of vulvar carcinomas, whereas low nuclear pCHK1Ser317, pCHK1Ser296, and pCHK1Ser280 expressions were observed in 58%, 64%, and 40% of the cases, respectively. Low levels of pCHK1Ser317 and pCHK1Ser280 in the nucleus correlated significantly with advanced tumor behaviors and aggressive features. None of pCHK1Ser345, pCHK1Ser317, pCHK1Ser296, and pCHK1Ser280 forms were identified as prognostic factors. In vitro inhibition of CHK1 by small molecular inhibitors or siRNA reduced viability by inducing DNA damage and apoptosis of vulvar cancer cell lines. In summary, we conclude that cellular functions regulated by CHK1 are phosphorylation/localization‐dependent and deregulation of CHK1 function occurs in VSCC and might contribute to tumorigenesis. Targeting CHK1 might represent as a useful antitumor strategy for the subgroup of VSCC harboring p53 mutations.

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Local and regional recurrence of vulval cancer: management dilemmas

Cited by 65 publications

References 47 publications

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

Characterization of Sociodemographic and Clinicopathological Features in Brazilian Patients with Vulvar Squamous Cell Carcinoma

Evaluation of CHK1 activation in vulvar squamous cell carcinoma and its potential as a therapeutic target in vitro

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