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ORIGINAL ARTICLE  
Year : 2022  |  Volume : 65  |  Issue : 4  |  Page : 828-831
Prognostic significance of mast cells and vascular density in prostatic adenocarcinoma


1 Department of Pathology, Heritage Institute Of Medical Sciences, Varanasi, Uttar Pradesh, India
2 Department of Pathology, Institute of Medical Sciences, B. H. U., Varanasi, Uttar Pradesh, India

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Date of Submission26-Jan-2021
Date of Acceptance24-May-2021
Date of Web Publication02-Jun-2022
 

   Abstract 


Context: Though mast cells infiltrate solid tumors, the exact role of mast cells in tumor biology is controversial. Mast cell density (MCD) may vary depending on its location in the tumor and tumor vascularity. MCD may influence the tumor aggressiveness. Aims: This study evaluates MCD and tumor vascularity in different histopathological grades of adenocarcinoma prostate. Settings and Design: Descriptive study with purposive sampling. Methods and Material: The subjects of study were 42 adenocarcinoma patients. 20 cases were of intermediate grade (Gleason score 2–7) and 22 were of high-grade (Gleason score 8-10). Histological diagnosis was made by examining sections stained with hematoxylin and eosin. Additional sections from the same block were stained for mast cells using Giemsa stains as per standard protocol. Mast cell count was done in minimum six random high-power microscopy fields in four different regions- intratumoral, peritumoral, stromal and perivascular regions. Statistical Analysis Used: SSPS software version 13.0. Descriptive statistics, Student's t test and ANOVA test. Results: In high-grade adenocarcinoma, mast cell counts were higher in perilesional, stromal and perivascular regions, whereas it was lower in intralesional areas as compared to the intermediate grade. However, statistical significance was observed only for the perivascular region. There was significantly higher number of blood vessels in high-grade adenocarcinoma as compared to intermediate grade adenocarcinoma. Conclusions: In this study, perilesional mast cells and vascularity increased with increased severity of adenocarcinoma. These findings suggest a possible influence of mast cells on the tumor microenvironment such as vessel density and aggressiveness of tumor. However, further studies are required to substantiate results of this study.

Keywords: Gleason score, mast cell density, prostatic adenocarcinoma, vascularity

How to cite this article:
Das B, Mendonca SM. Prognostic significance of mast cells and vascular density in prostatic adenocarcinoma. Indian J Pathol Microbiol 2022;65:828-31

How to cite this URL:
Das B, Mendonca SM. Prognostic significance of mast cells and vascular density in prostatic adenocarcinoma. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Nov 30];65:828-31. Available from: https://www.ijpmonline.org/text.asp?2022/65/4/828/346519





   Introduction Top


Many studies have shown that mast cells infiltrate solid tumors.[1] Mast cell role in the tumor biology is still controversial as some authors opine that mast cells have a pro-tumorigenic role and mast cell targeting hampers growth of prostate adenocarcinomas, whereas others are of the opinion that mast cells have an anti-tumorigenic role.[2],[3],[4] Another school of thought indicated that role of mast cell in tumor depends on the location of mast cell.[4] Authors have also tried to correlate the mast cell numbers with density of microvessel.[5] With Prostate cancer being second most common cancer in males and incidence of castration resistant prostate carcinoma high, a novel method of treatment of prostate carcinoma will prove to be indispensable.[6] Mast cell provides one such target but the challenge is to ascertain the actual role of mast cells, whether this role is influenced by its location in and around tumor tissue and the influence of tumor microenvironment. So this study was designed to correlate mast cell numbers and density of microvessels with Gleason's grading of prostatic adenocarcinoma.


   Subjects and Methods Top


Forty two patients of adenocarcinoma were the subjects of the study. Benign prostatic hyperplasia (BPH), inflammatory conditions of prostate such as prostatitis and other malignancies of prostate such as sarcoma, transitional cell carcinoma etc., were excluded from the study. This was a descriptive study with purposive sampling. The prostatic specimens including prostatic biopsies, transurethral resection of prostate (TURP) chips and excision biopsies of prostate were examined histopathologically. The specimens collected were fixed in 10% formalin for 12 to 24 hours before processing in an automatic sample processor after grossing. Sections of 4 μm thick were cut with a rotary microtome. Histological diagnosis was made by examining sections stained with hematoxylin and eosin (H and E). Additional sections from the same block were stained for mast cells using Giemsa stains as per standard protocol. Mast cell count was done in minimum six random high-power microscopy fields in four different regions - intratumoral, peritumoral, stromal and perivascular regions. Measurement of microvascular density was done by scanning the H and E stained slides at low magnification (×100). Areas with highest number of microvessels were chosen. Microvessels were counted in six high-power fields and mean microvascular density was calculated. Gleason scoring was done for all adenocarcinoma cases and graded as low grade (2–4), intermediate grade (5–7) and high grade (8–10). All the data was entered into Microsoft Excel 2010 spread sheet and analyzed using SSPS software version 13.0. Descriptive statistics were derived using frequency, percentage, mean, standard deviation. Student's t test and ANOVA test were used to test the significance, that is, nominal significance at P value ≤ 0.05 levels, and the P value > 0.05 was not significant.


   Results Top


Prostatic specimens of 42 adenocarcinoma patients were examined histopathologically for the distribution of mast cells in different regions according to severity. The mean age of the patients was 71.21 (±8.9) years. There were 20 patients of Intermediate grade (Gleason score 5-7) and 22 patients of high-grade (Gleason score 8–10) adenocarcinoma.

The number of mast cells in different regions, blood vessels and mast cells per blood vessel according to severity are depicted in [Table 1]. In high-grade adenocarcinoma, the mast cell counts were higher in peritumoral [Figure 1], stromal and perivascular [Figure 2] regions, whereas it was lower in intratumoral areas when compared with intermediate grade adenocarcinoma. However, statistical significance was observed only for the perivascular region (P = 0.013). There was significantly higher number of blood vessels in high-grade adenocarcinoma as compared to intermediate grade adenocarcinoma. However, number of mast cells per blood vessel was comparable.
Figure 1: Photomicrograph showing peritumoral mast cells in Prostate adenocarcinoma (Giemsa stain, 400x)

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Figure 2: Photomicrograph showing perivascular mast cells in Prostate adenocarcinoma (Giemsa stain, 400x)

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Table 1: Number of mast cells, blood vessels and mast cells per blood vessel (Mean±1 SD) according to severity (Gleason grading) of adenocarcinoma

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   Discussion Top


The main observations of this study are that the mast cells were mainly concentrated in the perilesional, stromal and perivascular regions of adenocarcinoma, whereas only few mast cells were observed inside the lesion. As the severity increased (high Gleason score), the intralesional mast cells were further reduced, whereas the perilesional mast cells increased. Similar was the observations of Nonomura et al.,[7] where the authors reported that the mast cell count was higher around cancer foci in patients with higher Gleason scores than in those with low Gleason scores. Sari et al.[8] found a significant difference between number of mast cells within and around the lesion. The authors hypothesized that the decrease in Mast cells in the tumor in advanced stages may be due to the degranulation of mast cells as the tumor grows as mast cell degranulation is common feature of later stage of tumor proliferation.

This study showed significantly higher microvessel density in the group with high Gleason score. Stawerski et al.[5] found significant positive correlations between the mean number of mast cells and microvessel density both in the group with prostate cancer and in the control group. In the patients with prostate cancer, a significant positive correlation was observed between the mean number of mast cells and Gleason score, as well as between microvessel density and Gleason score. Ahmadi et al.[9] found increased microvessel density in high-grade prostate cancer (grade 4 or 5) as compared to low grade (grade 2 or 3) prostate cancer.

Increased mast cell density (MCD) is associated with a poor prognosis in many cancers including Hodgkin's lymphoma, melanoma, endometrial, cervical, esophageal, lung, gastric, colorectal and prostate carcinomas.[10] The tumor promoting capacity of mast cells has been attributed to their release of proangiogenic and tissue degrading mediators as mast cell infiltration positively correlates with microvessel density and tumor progression.[11]

Johansson et al.[12] studied mast cell distribution in different compartments of prostatic cancer and observed that intra-tumoral mast cells negatively regulate angiogenesis and tumor growth, whereas peritumoral mast cells stimulate the expansion of human prostate tumors. Peritumoral mast cells provide Fibroblast Growth Factor-2 (FGF-2) to the tumor micro environment, which may contribute to their stimulating effect on angiogenesis.

Aydin et al.[13] observed significant difference between MCD of intralesional and perilesional region. However, the authors found no statistical difference between Gleason score groups. Fleischmann et al.[14] observed that high intratumoral MCD is associated with favorable tumor characteristics (Low Gleason score) and good prognosis in prostate cancer than tumors with low mast cell densities. Prostate-specific antigen recurrence-free survival significantly (P = 0.0001) decreased with decline of MCD showing poorest outcome for patients without intra-tumoral mast cells. This finding is consistent with a role of mast cells in the immunological host-defense reaction on prostate cancer. In this study also the intra-tumoral mast cells decreased in number as the severity increased defined by high Gleason score. Tóth-Jakatics et al.[15] found that mast cell number was significantly higher in high malignancy group. Invasion margin showed rich capillary network. Mast cells were located in peritumoral connective tissue most frequently around small blood vessels. According to Gleason's classification of these cases, highest number of vessels were found around high-grade malignancy tumors and there was significant correlation between the number of mast cells and capillary density. These findings are somewhat similar to the results of this study. Johansson et al.[12] found that in both nonmalignant and malignant human prostate tissue, mast cells were found principally in the stroma. In prostate tumors only a few mast cells were detected in the epithelial compartment. They also found that the mean number of mast cells in the nonmalignant stroma was significantly higher than in the tumor stroma. Globa et al.[16] found that in adenocarcinoma cases, MCD decreased in the intratumoral versus peritumoral areas. The mast cells are arranged around the epithelial tumor cell area and rarely intraepithelially, as well as in close vicinity to blood vessels. Peritumoral MCD correlated partially with Gleason score.


   Conclusion Top


In this study, perilesional mast cells as well as vascularity increased with increased severity of adenocarcinoma. These findings suggest a possible influence of mast cells on the tumor microenvironment such as vessel density and aggressiveness of tumor. However, further studies are required to substantiate the present results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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2.
Crivellato E, Nico B, Ribatti D. Mast cell contribution to tumor angiogenesis: A clinical approach. Eur Cytokine Netw 2009;20:197-206.  Back to cited text no. 2
    
3.
Pittoni P, Tripodo C, Piconese S, Mauri G, Parenza M, Rigoni A, et al. Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res 2011;71:5987-97.  Back to cited text no. 3
    
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Conti P, Castellani ML, Kempuraj D, Salini V, Vecchiet J, Tetè S, et al. Role of mast cells in tumor growth. Ann Clin Lab Sci 2007;37:315-22.  Back to cited text no. 4
    
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Stawerski P, Wagrowska-Danilewicz M, Stasikowska-Kanicka O, Tuka E, Danilewicz M. Augmented mast cell infiltration and microvessel density in prostate cancer. Contemp Oncol 2013;17:378–82.  Back to cited text no. 5
    
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Li L, Dang Q, Xie H, Yang Z, He D, Liang L, et al. Infiltrating mast cells enhance prostate cancer invasion via altering LncRNA-HOTAIR/PRC2-androgen receptor (AR)-MMP9 signals and increased stem/progenitor cell population. Oncotarget 2015;6:14179-90.  Back to cited text no. 6
    
7.
Nonomura N, Takayama H, Nishimura K, Oka D, Nakai Y, Shiba M, et al. Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer. Br J Cancer 2007;97:952–6.  Back to cited text no. 7
    
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Sari A, Serel TA, Candir O, Oztürk A, Kosar A. Mast cell variations in tumour tissue and with histopathological grading in specimens of prostatic adenocarcinoma. BJU Int 1999;84:851-3.  Back to cited text no. 8
    
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Ahmadi SA, Moinfar M, Gohari Moghaddam K, Bahadori M. Practical application of angiogenesis and vasculogenic mimicry in prostatic adenocarcinoma. Arch Iran Med 2010;13:498-503.  Back to cited text no. 9
    
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Groot Kormelink T, Abudukelimu A, Redegeld FA. Mast cells as target in cancer therapy. Curr Pharm Des 2009;15:1868-78.  Back to cited text no. 10
    
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Ribatti D, Vacca A, Ria R, Marzullo A, Nico B, Filotico R, et al. Neovascularisation, expression of fibroblast growth factor-2, and mast cells with tryptase activity increase simultaneously with pathological progression in human malignant melanoma. Eur J Cancer 2003;39:666-74.  Back to cited text no. 11
    
12.
Johansson A, Rudolfsson S, Hammarsten P, Halin S, Pietras K, Jones J, et al. Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am J Pathol 2010;177:1031-41.  Back to cited text no. 12
    
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Aydin O, Dusmez D, Cinel L, Doruk E, Kanik A. Immunohistological analysis of mast cell numbers in the intratumoral and peritumoral regions of prostate carcinoma compared to benign prostatic hyperplasia. Pathol Res Pract 2002;198:267-71.  Back to cited text no. 13
    
14.
Fleischmann A, Schlomm T, Köllermann J, Sekulic N, Huland H, Mirlacher M, et al. Immunological microenvironment in prostate cancer: High mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate 2009;69:976-81.  Back to cited text no. 14
    
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Tóth-Jakatics R, Jimi S, Takebayashi S, Kawamoto N. Cutaneous malignant melanoma: Correlation between neovascularization and peritumor accumulation of mast cells overexpressing vascular endothelial growth factor. Hum Pathol 2000;31:955-60.  Back to cited text no. 15
    
16.
Globa T, Saptefrţi L, Ceauşu RA, Gaje P, Cimpean AM, Raica M. Mast cell phenotype in benign and malignant tumors of the prostate. Pol J Pathol 2014;65:147-53.  Back to cited text no. 16
    

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Correspondence Address:
Bismay Das
Heritage Institute of Medical Sciences, NH-2, Bhadwar, Varanasi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpm.ijpm_93_21

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