Periapical odontogenic granulomas are among the most encountered pathology that involve the alveolar bone, with severe consequences such as bone resorption, the presence of inflammatory infiltrate and the formation of abnormal vascularization. The present study aimed to quantify the existence of the microvessel density (MVD), mast cell density (MCD) and heterogeneity of the encountered blood vessels. A total of 37 patients diagnosed with odontogenic periapical granulomas were included, and the gender distribution, age and localization of the pathological lesions was assessed. After the surgical removal of the periapical odontogenic granuloma, the collected tissue was fixed in 10% buffered formalin. Primary processing, morphological analysis and immunohistochemical staining was performed in order to characterize the altered tissue. The results outlined the presence of a high number of mast cells, especially in the area of the inflamed tissue; the high heterogeneity of the blood vessels; and increased MVD with positive CD34. The conclusions of the study focus on the key role of the mast cells and their implication in the initiation and development of the angiogenesis process, triggering the inflammatory response of the host. Nevertheless, periapical odontogenic granulomas develop as an inflammatory response to the interaction between the host’s immune system and microbial invasion.

Human Periapical Odontogenic Granulomas: Aspects of Microvessel Density (MVD), Heterogeneity of Blood Vessels and Mast Cells Density (MCD)

The main mechanism of the formation of granulation tissue is the progression of an infection from the tooth to the periapical bone. At this level, the immune system tries to localize and annihilate the microorganism's injury. Ki-67 is a protein directly associated with the cell proliferation rate, while CD34 is a biomarker involved in angiogenesis, and studies suggest that they both have a positive correlation with the intensity of the local inflammatory infiltrate. This study will determine the immunoexpression of CD34 and Ki-67 in periapical granulomas and assess their impact on the growth and development of this tissue, as well as consider their roles in the proliferative process and aggressiveness of evolution. 

CD34 and Ki-67 Immunoexpression in Periapical Granulomas: Implications for Angiogenesis and Cellular Proliferation

Tumors and cysts with odontogenic origin represent a family of lesions with specific histo-genetic and clinical characteristics. Among them, ameloblastomas are common benign neoplasms, predominantly detected in the anatomic areas of the jaws and also in the mandible and maxilla. Although they are characterized by a slow and stable growing pattern, a subset of them shows a tendency for local tissue invasiveness and partially increased recurrence rates after surgical excision. Furthermore, heat shock proteins (HSPs) are potentially implicated in ameloblastoma onset and progression. HSPs regulate the folding and refolding of proteins and are induced in response to oxidative stress. They are crucial members of the chaperone intracellular system and are categorized based on their molecular weight (i.e., HSP27, HSP60, HSP70, HSP90). In the current review, we describe HSPs origin and function, focusing on their deregulation mechanisms and impact predominantly on ameloblastomas and also on inflammatory and developmental odontogenic cystic lesions. 

Heat Shock Proteins' Expression Profiles in Odontogenic Ameloblastomas and Cysts.

Background/Aim: Neo-lymphangiogenesis induces lymphatic invasion of cancer cells, significantly increasing the metastatic potential of breast carcinomas (BCs). Among the molecules that are implicated in lymphangiogenesis, podoplanin (PDPN, gene locus: 1p36.21) - a transmembrane receptor glycoprotein - is expressed exclusively in lymphatic vessels. The current study explored the impact of PDPN-dependent mean lymphatic micro-vessel density (mLMVD) in invasive ductal (inDBC) and invasive lobular breast adenocarcinomas (inLBC). Materials and Methods: A set of thirty (n=30) paraffin-embedded invasive BC tissue sections (22 inDBCs and 8 inLBCs, respectively) were analyzed by applying a combination of immunocytochemistry (IHC) and digital image analysis (DIA) assays. Results: High and moderate mLMVD rates (defined by the mean number of lymphatic domains with emboli in five optical fields under 400X magnification) were detected in 5/30 (16.6%) and 6/30 (20%) cases (total 11/30 (36.6%), respectively. In these cases, PDPN demonstrated strong cytoplasmic/membranous staining intensity. The remaining 19 cases (63.4%) demonstrated low levels of mLMVD. mLMVD was significantly correlated with the stage of the examined malignancies (p=0.019), whereas a marginal association with the grade of differentiation was identified (p=0.042). No significant correlation was observed with histological subtype (p=0.234) or tumor size (p=0.085). Conclusion: Neo-lymphangiogenesis in BCs is a critical histological feature in the progression of the malignancy and is correlated with an aggressive phenotype (advanced stage). PDPN expression in lymphatic micro vessels is a reliable biomarker for evaluating lymphangiogenic activity in BCs, independently of their histotype, especially when assessed with precise DIA techniques. 

pdf/podoplanin-related-lymphatic-micro-vessel-density-digital-nl03vu0ai7p9.pdf

Podoplanin – Related Lymphatic Micro Vessel Density Digital Analysis in Breast Adenocarcinoma

BACKGROUND/AIM
Odontogenic cysts belong to a type of lesions with endodontic origin that in some cases mimic even aggressive odontogenic tumors sharing with them similar radiographic features. Periapical cysts (PCs) belong to the inflammatory odontogenic cysts sub-category and rarely squamous cell carcinoma arises from their hyperplastic/ dysplastic epithelia. This study aimed to explore the impact of cluster differentiation 34 (CD34) protein expression combined with micro vessel density (MVD) on PCs.


MATERIALS AND METHODS
Forty-eight (n=48) archival, formalin-fixed, and paraffin-embedded PC tissue specimens were included in the study. Immunohistochemistry (IHC) was performed in the corresponding tissue sections using an anti- CD34 antibody. CD34 expression levels and also MVD in the examined cases were measured by implementing a digital image analysis protocol.


RESULTS
CD34 over-expression (moderate to high staining intensity levels) were detected in 29/48 (60.4%) cases, whereas the rest of them (19/48-39.6%) were characterized by low levels of expression. Extended MVD was identified in 26/48 (50.1%) cases correlated with CD34 over-expression, epithelial hyperplasia (p-value=0.001), and marginally with inflammatory infiltration level in the examined lesions (p-value=0.056).


CONCLUSION
CD34 over-expression combined with increased MVD is associated with a neoplastic-like (hyperplastic) phenotype in PCs as a result of increased neo-angiogenic activity. These histopathological characteristics rarely form an eligible substrate for squamous cell carcinoma onset in untended cases.

https://www.cancerdiagnosisprognosis.org/storage/cdp/3/2/cdp-3-189.pdf

Impact of CD34-dependent Micro Vessel Density on Periapical Odontogenic Cysts.

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Impact of CD34-dependent Micro Vessel Density on Periapical Odontogenic Cysts.

Heat Shock Proteins' Expression Profiles in Odontogenic Ameloblastomas and Cysts.