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Keratin pearl degradation in oral squamous cell carcinoma: reciprocal roles of neutrophils and macrophages
Author(s) -
Essa Ahmed A. M.,
Yamazaki Manabu,
Maruyama Satoshi,
Abé Tatsuya,
Babkair Hamzah,
Cheng Jun,
Saku Takashi
Publication year - 2014
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12197
Subject(s) - keratin , basal cell , medicine , immunology , pearl , pathology , cancer research , philosophy , theology
Background We have reported that neutrophilic infiltration was associated with round‐shaped dyskeratosis foci, a kind of keratin pearl, of oral carcinoma in situ and that those inflammatory cells are recruited from intra‐epithelially entrapped blood vessels. Based on these lines of evidence, we have formulated a hypothesis that keratin pearls are terminally degraded by neutrophils. To confirm this hypothesis, we investigated immunohistochemically stepwise degradation of keratin pearls in oral squamous cell carcinoma ( SCC ) to clarify any other type scavenger cells in addition to neutrophils are involved in this particular degradation process. Methods Neutrophils (neutrophil elastase) and macrophage subpopulations ( CD 68, CD 163 and CD 204) were immunohistochemically localized in 30 cases of oral SCC with typical round‐shaped keratin pearls. SCC cells were revealed by immunohistochemistry for keratin (K) 17, and blood vessels were demonstrated by CD 31. Results Keratin pearl degradation process was divided into four steps: (i) intact stage: no macrophage infiltration but minimal neutrophils were found in keratin pearls; (ii) neutrophil recruit stage: no macrophage infiltration but focal neutrophilic infiltration within the pearls; (iii) neutrophil predominant stage: dense neutrophil infiltration with minimal macrophages and segregated keratinized cancer cells strongly positive for K17; and (iv) macrophage predominant stage: dense infiltration of CD 68‐, CD 163 (mononuclear)‐ and CD 204 (multinucleated)‐positive macrophages engulfing detached keratinized SCC cells. Conclusion Keratin pearl degradation in oral SCC is strictly regulated by two types of scavenger cells: neutrophils, which perform initial tasks, and macrophages, which reciprocally take over from neutrophils the role to finalize the degradation processes.