Elsevier

The Surgeon

Volume 11, Issue 3, June 2013, Pages 147-152
The Surgeon

An analysis of microvessel density in salivary gland tumours: A single centre study

https://doi.org/10.1016/j.surge.2012.07.004Get rights and content

Abstract

Backgrounds

Microvessel density (MVD) can be used for determining neoplastic neovascularisation. Tumour angiogenesis correlates with prognosis of cancers in many organs. The aims of this study were to evaluate MVD as demonstrated by CD31 and CD105 in salivary gland tumours (SGTs), and to correlate the MVD results with clinicopathological characteristics of the tumours.

Materials and methods

Using a retrospective cohort study design, we enrolled SGTs patients at the Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand, over the 22-year period. The predictor variables included demographic, anatomic and histopathological parameters. The outcome measure was average CD31-MVD and CD105-MVD counted by the “hot spot” method. Descriptive, uni- and bivariate statistics were computed, and P <0.05 was considered statistically significant.

Results

The study sample consisted of 43 subjects with a mean age of 39.6 ± 17.8 years (range, 9–82), including 26 females (60.5%), diagnosed with SGTs. In this cohort, 58.1% of the cases were benign, and 83.7% were minor SGTs. There was a significant correlation between CD31-MVD and CD105-MVD (r = 0.8, P < 0.001), but mean CD31-MVD and CD105-MVD were 17.7 ± 9.3 and 12.8 ± 7.4, respectively (P = 0.009). Age, gender and tumour site were not individually associated with significant differences between CD31-MVD and CD105-MVD. Tumours with myoepithelial cells had lower MVD than those without myoepithelial cells (P = 0.04 for CD31; P = 0.03 for CD105). Only CD105-MVD showed statistical difference between benign and malignant SGTs (P = 0.01).

Conclusions

These results suggest that MVD in SGTs can be demonstrated by CD31 and CD105. Despite a strong correlation, CD31-MVD is always higher than CD105-MVD and cannot differentiate between benign and malignant SGTs. The presence of myoepithelial cells within SGTs affects the MVD analysis using either CD31 or CD105, while age, gender and tumour location do not.

Introduction

Angiogenesis is neovascularisation derived from pre-existing vasculature.1 It is necessary for tumour growth, invasion and metastasis because it delivers oxygen and nutrients and eliminates metabolic wastes.2, 3, 4, 5, 6 Oxygen diffuses maximally 200–250 μm from blood vessels.2 A hypoxic tumour cannot enlarge its size >2–3 mm3. Once a growing tumour lacks blood supply, central necrosis begins.1, 7 Both tumour cells and stromal cells of solid tumours are sources of angiogenic factors alike.8 The neovascularisation is regulated by a series of interrelated events. The complex interplay between proangiogenic and antiangiogenic factors tightly controls tumour angiogenesis.9, 10 Tumour angiogenesis is therefore achieved by altering the balance between angiogenic stimulation and inhibition in the local environment.6

The angiogenesis of tumours can be measured by the amount of blood vessels.11 In 1991, Weidner et al.12 introduced the “hot spot” method for counting microvessel density (MVD) in breast cancer. Since then, this technique has been widely used for determining neoplastic neovascularisation. Tumour angiogenesis correlates with prognosis of cancers in many organs, such as breast,13 lung,14 stomach,15 colon,16 cervix,17 and urinary bladder.18 We recently reported the MVD of head and neck lesions of Kimura's disease.19 In oral squamous cell carcinoma patients, the presence and distribution pattern of CD34 around tumour blood vessels, which is related to over-expression of the tumour suppressor-gene p53, are associated with recurrence, early metastasis to lymph nodes and death.6 So far angiogenesis of salivary gland tumours (SGTs) measured by MVD has received limited attention. Very few studies analysed a wide range of SGTs.20, 21

The main purpose of the present study was to evaluate the microvessels in SGTs, which was identified by antibodies to CD31 and CD105 (CD31-MVD and CD105-MVD). Our secondary aim was to compare the CD31-MVD and CD105-MVD in relation to the demographic, anatomic and histopathological parameters.

Section snippets

Study design/sample

To address the research goals, we used a retrospective cohort study design. The sample was derived from patient data presenting to Department of Oral Pathology, Chulalongkorn University, for diagnosis of SGTs from January 1, 1988, to December 31, 2009. To identify eligible study samples, we searched the departmental registries. Those with histologically confirmed SGTs and available pathology records and specimens were included in the study sample. Patients without sufficient records, and those

Results

From 1988 to 2009, 43 cases met the inclusion criteria for this study. The mean age was 39.6 ± 17.8 years (range, 9–82); 26 patients (60.5%) were females. Of the 43 subjects, only 7 cases (16.3%) had a major SGT and 18 SGTs (41.9%) were malignant. They were 21 pleomorphic adenomas (48.8%), 2 Warthin's tumours (4.65%), 2 basal cell adenomas (4.65%), 8 mucoepidermoid carcinomas (18.6%), 9 adenoid cystic carcinomas (20.9%) and 1 myoepithelial carcinoma (2.3%).

The microvessels in SGTs were clearly

Discussion

The present study sought to evaluate CD31-MVD and CD105-MVD in SGTs and to compare both of them in relation to the demographic, anatomic and histopathological parameters. We analysed the CD31-MVD and CD105-MVD in 43 SGTs, and correlated their expression with 5 predictor variables: gender, age, tumour location and type, and the presence of myoepithelial cells.

Our results showed that CD31-MVD was always higher than CD105-MVD (P = 0.009), even though both markers had a strong correlation (r = 0.8,

Conclusions

Although malignant SGTs show higher MVD than benign SGTs, not all of them possess high MVD. Consequently, MVD could not be an indicator to distinguish between benign and malignant SGTs. The presence of myoepithelial cells affects the MVD analysis, while age, gender and tumour location do not. Future researches should be done in a larger sample to investigate MVD of each histopathological SGT subtypes, and to develop antiangiogenic therapy, especially in SGTs with high MVD, into an alternative

Ethical approval

Approved (protocol No. 29/2007).

Funding

Research fund from Faculty of Dentistry, Chulalongkorn University, Thailand.

Authorship disclosure

Kittipong Dhanuthai: Conception, design, definition of intellectual content, literature search, experimental studies, acquisition and analysis of data, statistical analysis, manuscript preparation, manuscript editing, and manuscript review.

Kraisorn Sappayatosok: Conception, design, definition of intellectual content, literature search, experimental studies, acquisition of data, statistical analysis, manuscript editing, and manuscript review.

Somchai Yodsanga: Conception, design, experimental

Conflict of interest

The authors indicate full freedom of investigation and no potential conflicts of interest.

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