Histology and histopathology Vol.36, nº3 (2021)

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Open Access
The pathogenesis and pathology of idiopathic pleuroparenchymal fibroelastosis
(2021) Kinoshita, Yoshiaki; Ishii, Hiroshi; Nabeshima, Kazuki; Watanabe, Kentaro
Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare subtype of idiopathic interstitial pneumonias that consists of elastofibrosis involving the lung parenchyma and pleural collagenous fibrosis predominantly located in the upper lobes. IPPFE has various distinct clinical and physiological characteristics, including platythorax and a marked decrease of forced vital capacity with an increased residual volume on a respiratory function test. The concept of IPPFE is now widely recognized and some diagnostic criteria have been proposed. In addition, the accumulation of cases has revealed the pathological features of IPPFE. However, little is known about the pathogenesis or the process of disease formation in IPPFE. This review article will provide a summary of the pathological features and previously reported hypotheses on disease formation in IPPFE, to discuss the potential etiologies and pathogenesis of IPPFE.
Open Access
Shufeng Jiedu capsules protect rats against LPS-induced acute lung injury via activating NRF2-associated antioxidant pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Liao, Qingwu; Chen, Wenan; Tong, Zhufeng; Xue, Mingming; Gu, Tianwen; Yuan, Ying; Song, Zhenju; Tao, Zhengang
Shufeng Jiedu capsule (SFJDC) is a traditional Chinese medicine, which has been used for the treatment of respiratory infections for more than thirty years in Hunan (China). SFJDC protected rats against LPS-induced acute lung injury (ALI); however, the molecular mechanisms underlying the therapeutic effects of SFJDC remain unclear. Therefore, this study aimed at analyzing the major anti-inflammatory compounds of SFJDC and exploring the underlying molecular mechanisms. SFJDC dissolved in water was fingerprinted by UPLC/Q-TOF. Inflammation response was assessed by histopathological examination and ELISA assay. Arterial blood gases were also analyzed to evaluate the function of rat lungs. The expression levels of Kelch-like ECH-associating protein 1 (Keap1), Nrf2, heme oxygenase-1 (HO1), Cullin 3 (CUL3) and NQO1 were analyzed by Western blotting. Results indicated that SFJDC alleviated inflammation response by reducing the level of inflammatory cytokines, and upregulation of glutathione-S-transferase (GST) and superoxide dismutase (SOD) in lung tissues. Furthermore, SFJDC suppressed LPS-induced upregulation of Keap 1 and CUL3 in rat lungs. The expression of NRF2 HO1 and NQO1 were further upregulated by SFJDC in the presence of LPS, indicating that SFJDC might activate the NRF2- associated antioxidant pathway. In conclusion, SFJDC treatment may protect the rat lungs from LPS by alleviating the inflammation response via NRF2- associated antioxidant pathway
Open Access
Implications of androgen receptor and FUS expression on tumor progression in urothelial carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Abd Raboh, Nermine Mohamed; Adel Hakim, Sarah; Abd El Atti, Rasha Mohamed
Androgen receptor (AR) interact with many pathways involved in bladder cancer development and progression. FUS (fused in liposarcoma), a multifunctional protein essential for different cellular processes, has been demonstrated as a key link between androgen receptor signaling and cell-cycle progression in prostate cancer but has not been examined in urothelial carcinoma (UC) despite an intimate association between prostate and bladder carcinogenesis. Aim. to examine the immunohistochemical expression of AR and FUS in urothelial carcinoma in relation to prognostic parameters and to extrapolate any possible link between the expression of both markers and tumor progression. Study design. Retrospective study using immunohistochemical staining for AR and FUS on (88) cases of urothelial carcinoma. Results. AR shows statistically significant relations with late tumor stage, high tumor grade, and nonpapillary tumor pattern. On the other hand, FUS expression correlates with early tumor stage, low tumor grade and papillary pattern. An inverse relation is found between AR and FUS expression (p=0.001). Cases with high AR IHC expression show statistically significant shorter OS, RFS and PFS compared to cases with low AR expression. Cases with high FUS IHC expression reveal statistically significant longer OS, RFS and PFS compared to cases with low FUS expression. Conclusion. FUS expression is associated with favorable prognostic parameters of UC. A possible interaction is suggested between FUS and AR pathways involved in urothelial cancer progression. Manipulating FUS levels and androgen deprivation therapy can provide new promising targets for treatment trials.
Open Access
Frequent DYRK2 gene amplification in micropapillary element of lung adenocarcinoma - an implication in progression in EGFR-mutated lung adenocarcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Koike, Chihiro; Okudela, Koji; Matsumura, Mai; Mitsui, Hideaki; Suzuki, Takehisa; Arai, Hiromasa; Kataoka, Toshiaki; Ishikawa, Yoshihiro; Umeda, Shigeaki; Tateishi, Yoko; Ohashi, Kenichi
The present study aimed to discern the molecular alterations involved in the progression of EGFR-mutated lung adenocarcinoma (LADC). We previously demonstrated that the micropapillary (mPAP) element is the most important histological factor for assessing malignant grades in LADCs. Therefore, mPAP and other elements were separately collected from three cases of EGFR-mutated LADC using laser capture microdissection and subjected to a comprehensive mRNA expression analysis. We focused on DYRK2 in this study because its level showed a substantial increase in EGFR-mutated LADCs with mPAP. We also immunohistochemically examined 130 tumors for the expression of DYRK2. The results confirmed a strong expression of DYRK2 in EGFR-mutated LADC with mPAP. Fluorescent in situ hybridization (FISH) analyses targeting the DYRK2 locus revealed frequent gene amplification in EGFR-mutated LADC, specifically occurring in the high-grade components, like mPAP. In summary, the results of this study suggest that DYRK2 overexpression through gene amplification is one of the molecular mechanisms responsible for promoting the progression of EGFR-mutated LADC.
Open Access
Exposure to second-hand cigarette smoke exacerbates the progression of osteoarthritis in a surgical induced murine model
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Rose, Brandon J.; Weyand, Jeffery A.; Liu, Brady; Smith, Jacob F.; Perez, Brian R.; Clark, J. Christian; Goodman, Michael; Budge, Kelsey M. Hirschi; Eggett, Dennis L.; Arroyo, Juan A.; Reynolds, Paul R.; Kooyman, David L.
Osteoarthritis (OA), formerly understood to be a result of passive wear, is now known to be associated with chronic inflammation. Cigarette smoking promotes systemic inflammation and has been implicated in increased joint OA incidence in some studies, though the recent observational data on the association are contradictory. We hypothesize that second-hand smoke (SHS) treatment will increase the incidence of OA in a mouse model that has been subjected to a surgical destabilization of the medial meniscus (DMM). To test this hypothesis, we applied either SHS treatment or room air (RA) to mice for 28 days post-DMM surgery. Histopathology findings indicated that the knees of SHS mice exhibited more severe OA than their control counterparts. Increased expression of matrix metalloprotease-13 (MMP-13), an important extracellular protease known to degrade articular cartilage, and nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB), an intracellular effector of inflammatory pathways, were observed in the SHS group. These findings provide greater understanding and evidence for a detrimental role of cigarette smoke on OA progression and systemic inflammation.
Open Access
Astrocyte phenotypes: Emphasis on potential markers in neuroinflammation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Bozic, Iva; Savic, Danijela; Lavrnja, Irena
Astrocytes, the most abundant glial cells in the central nervous system (CNS), have numerous integral roles in all CNS functions. They are essential for synaptic transmission and support neurons by providing metabolic substrates, secreting growth factors and regulating extracellular concentrations of ions and neurotransmitters. Astrocytes respond to CNS insults through reactive astrogliosis, in which they go through many functional and molecular changes. In neuroinflammatory conditions reactive astrocytes exert both beneficial and detrimental functions, depending on the context and heterogeneity of astrocytic populations. In this review we profile astrocytic diversity in the context of neuroinflammation; with a specific focus on multiple sclerosis (MS) and its best-described animal model experimental autoimmune encephalomyelitis (EAE). We characterize two main subtypes, protoplasmic and fibrous astrocytes and describe the role of intermediate filaments in the physiology and pathology of these cells. Additionally, we outline a variety of markers that are emerging as important in investigating astrocytic biology in both physiological conditions and neuroinflammation.
Open Access
MiR-590-5p regulates cell proliferation, apoptosis, migration and invasion in oral squamous cell carcinoma by targeting RECK
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Bao, Wei-Wei; Shi, You-Ling; Ma, Yan; Qu, Xing-Hui; Pang, Guang-Ming; Yang, Lei
Objective. To discover the role of miR-590- 5p in oral squamous cell carcinoma (OSCC) progression and the corresponding mechanism via the targeting RECK. Methods. OSCC (n=85) and normal oral tissues (n=60) were collected to quantify the miR-590-5p expression by using qRT-PCR. Then SCC-15 and OECM1 cells were selected and divided into Mock, inhibitor NC, miR-590-5p inhibitor, si-RECK and miR-590-5p inhibitor + si-RECK groups. Dual-luciferase reporter gene assay was used to verify if miR-590-5p could target RECK. The biological behaviors of OSCC cells were evaluated by MTT, Wound-healing, Transwell and Flow cytometry. The expression of miR-590-5p and RECK was measured by qRT-PCR and Western blotting, respectively. Results. Overexpression of miR-590-5p was found in OSCC tissues. The expression of miR-590-5p was significantly associated with the clinical TNM stage, differentiation degree, and lymph node metastasis of OSCC. RECK was identified as a direct target of miR590-5p. Compared with the Mock group, cells in the miR-590-5p inhibitor group were decreased in terms of proliferation, invasion, and migration, and increased in cell apoptosis, accompanied by down-regulated miR590-5p, Bcl-2/Bax and MMP-9, and up-regulated RECK. By contrast, si-RECK group presented completely opposite changes, and si-RECK reversed the inhibitory effect of miR-590-5p inhibitor on the OSCC cell growth. Conclusion. MiR-590-5p expression was obviously increased in OSCC, and inhibiting miR-590-5p enhanced the expression of its target gene RECK, thereby suppressing proliferation, migration and invasion of OSCC cells and promoting apoptosis of OSCC cells
Open Access
Anaplastic thyroid carcinoma: Updates on WHO classification, clinicopathological features and staging
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Abe, Ichiro; King-yin Lam, Alfred
Anaplastic thyroid carcinoma is an uncommon carcinoma representing 1 to 4% of all thyroid cancers. The carcinoma is most common in females of the eight decades. It is a locally advanced cancer with frequent infiltration of surrounding organs, blood vessels and skin of neck. Paraneoplastic manifestations could occur. Approximately half of the patients with anaplastic thyroid carcinoma had distant metastasis with lung and brain as the most frequent sites of metastasis. The median survival of patients with anaplastic thyroid carcinoma reported was from 1 to 6 months. The terminology of the cancer in World Health Organization is "anaplastic thyroid carcinoma" rather than "undifferentiated thyroid carcinoma". In the latest American Joint Committee on Cancer (AJCC) TNM staging system for anaplastic thyroid carcinoma, there are updates on T and N categories. To conclude, updated knowledge of clinicopathological features, classification, pathological staging will improve our understanding of the cancer and will help in the management of the patients with this aggressive cancer.
Open Access
Microtubule-associated proteins (MAPs) in microtubule cytoskeletal dynamics and spermatogenesis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Wang, Lingling; Yan, Ming; Wong, Chris K.C.; Ge, Renshan; Wu, Xiaolong; Sun, Fei; Yan Cheng, C.
The microtubule (MT) cytoskeleton in Sertoli cells, a crucial cellular structure in the seminiferous epithelium of adult mammalian testes that supports spermatogenesis, was studied morphologically decades ago. However, its biology, in particular the involving regulatory biomolecules and the underlying mechanism(s) in modulating MT dynamics, are only beginning to be revealed in recent years. This lack of studies in delineating the biology of MT cytoskeletal dynamics undermines other studies in the field, in particular the plausible therapeutic treatment and management of male infertility and fertility since studies have shown that the MT cytoskeleton is one of the prime targets of toxicants. Interestingly, much of the information regarding the function of actin-, MT- and intermediate filament-based cytoskeletons come from studies using toxicant models including some genetic models. During the past several years, there have been some advances in studying the biology of MT cytoskeleton in the testis, and many of these studies were based on the use of pharmaceutical/toxicant models. In this review, we summarize the results of these findings, illustrating the importance of toxicant/pharmaceutical models in unravelling the biology of MT dynamics, in particular the role of microtubule-associated proteins (MAPs), a family of regulatory proteins that modulate MT dynamics but also actin- and intermediate filamentbased cytoskeletons. We also provide a timely hypothetical model which can serve as a guide to design functional experiments to study how the MT cytoskeleton is regulated during spermatogenesis through the use of toxicants and/or pharmaceutical agents.
Open Access
Two updates on oesophagogastric junction adenocarcinoma from the fifth WHO classification: Alteration of definition and emphasis on HER2 test
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Li, Yunzhu; Li, Jiayu; Li, Jiman
Introduction. The incidence of oesophagogastric junction adenocarcinoma has increased rapidly but remains controversial over the last decades. There are two crucial updates of the fifth World Health Organization (WHO) classification, including the alteration of its definition and the emphasis on the human epidermal growth factor receptor 2 (HER2) test. Methods. A total of 566 clinicopathological samples from patients who were diagnosed with gastric adenocarcinoma were retrospectively analyzed. We comprehensively compared the clinicopathological features of oesophagogastric junction adenocarcinoma between the fourth (V4.0) and fifth (V5.0) WHO versions. The clinicalpathological features among oesophagogastric junction, proximal and distal gastric tumors with fourth and fifth edition were also compared, respectively. Also, we discuss the correlation of HER2- expression with clinicopathological features according to the V5.0. Results. The results showed that the difference was mainly between oesophagogastric junction and distal adenocarcinoma in V4.0, while some were found between proximal and distal adenocarcinoma in V5.0. Tumors invading the oesophagus more than 3cm were still mainly oesophagogastric junction tumors. The expression of HER2 in oesophagogastric junction and proximal gastric adenocarcinoma was still higher than that in gastric body and distal sites. Conclusions. The clinicopathological parameters of the oesophagogastric junction tumors changed to some extent in the updated WHO version. The proximal gastric tumors tended to be more invasive than those located in oesophagogastric junction. But the latter with oesophageal invasion required additional management. The HER2-expression of oesophagogastric junction adenocarcinoma is the highest. The classification of V5.0 is reasonable and worth recommendation

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