Annexin A2 Expression in Aerogenous Metastasis of Pulmonary Invasive Mucinous Adenocarcinoma: A Case Report including Immunohistochemical Analysis

Arai, Kazumori; Hirose, M

doi:10.1155/2019/5064852

Cited by 4 publications

(14 citation statements)

References 27 publications

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“…To the best of our knowledge, our report was the first to indicate the involvement of this protein in STAS/AM. In the reported case, tumor cell detachment occurred at the tip of a villousshaped tumor component that had projected into the alveolar spaces [9]. In contrast to our previous report, other researchers described tumor cell detachment from the basement membrane (BM) of the alveolar wall as a common origin of STAS/AM from IMAC [10,11].…”

Section: Introductioncontrasting

confidence: 59%

“…Invasive mucinous AC (IMAC) frequently progresses via STAS/AM [8]. Recently, we reported the expression of annexin A2 (ANX A2), which is a Ca 2+ /membrane-binding protein in a case of IMAC with STAS/AM [9]. To the best of our knowledge, our report was the first to indicate the involvement of this protein in STAS/AM.…”

Section: Introductionmentioning

confidence: 73%

“…In addition to a routine pathological analysis, tissue from the left-sided tumor was subjected to immunohistochemical analyses to detect the expression of various proteins, including ANX A2 and collagen IV. Immunohistochemistry was performed using Leica Bond-Max (Leica Biosystems, Australia) and a previously described ANX A2 antibody and staining protocol [9]. A mouse antihuman collagen IV antibody (clone CIV 22, DAKO, USA) was used as the primary antibody at a dilution ratio of 1 : 25 after a 5 min treatment with proteinase K. Only routine immunohistochemistry was performed on the right lung tumor because of the small amount of available tissue.…”

Section: Case Presentationmentioning

confidence: 99%

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Annexin A2 Expression in the Aerogenous Spread of Pulmonary Invasive Mucinous Adenocarcinoma with Gastric Lineage

Arai

Iwasaki

Tsuchiya

et al. 2020

Case Reports in Oncological Medicine

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Spread through air spaces (STAS) is a unique form of lung cancer progression associated with a worse prognosis. However, the mechanisms underlying STAS and the associated proteins remain unclear. Annexin A2 (ANX A2), which is a membrane-binding protein involved in cell adhesion, is known to promote cancer invasion. In this report, we describe the immunohistochemical analysis of ANX A2 expression in an invasive mucinous adenocarcinoma (IMAC) resected from a 63-year-old man in whom the tumor cells had detached from the alveolar wall and exhibited STAS. At the detachment site, we observed cytoplasmic ANX A2 positivity on the basal side and in the exfoliative gap, as well as reduced collagen IV positivity expression. This biomarker pattern suggested an IMAC with gastric lineage. We hypothesize that ANX A2 is secreted from the basal sides of tumor cells and induces tumor cell detachment by degrading the basement membrane. A further comparison of this case with an IMAC with nongastric lineage suggested the following probabilities: (1) ANX A2 likely contributes to STAS in a manner that is dependent on its subcellular localization. (2) Both the subcellular localization of ANX A2 and the detachment site depend on tumor cell characteristics, including the biomarker immunophenotype.

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Section: Introductioncontrasting

confidence: 59%

Section: Introductionmentioning

confidence: 73%

Section: Case Presentationmentioning

confidence: 99%

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Annexin A2 Expression in the Aerogenous Spread of Pulmonary Invasive Mucinous Adenocarcinoma with Gastric Lineage

Arai

Iwasaki

Tsuchiya

et al. 2020

Case Reports in Oncological Medicine

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“…Immunohistochemistry was performed with serial tissue sections, using Leica Bond-Max (Leica Biosystems, Australia). The characterization and staining protocol of each antibody for ANX A2 (catalogue number, 610068) and MUC-1 (catalogue number, NCL-MUC-1) have been described previously [ 16 , 17 ]. Mouse anti-human EMA antibody (clone, GP 1.4; catalogue number, NCL-EMA; Leica Microsystems, UK) was used at a dilution ratio of 1 : 500, after a 10 min heat antigen retrieval with a citrate-based solution (pH 6.0).…”

Section: Case Presentationmentioning

confidence: 99%

Involvement of Annexin A2 Expression and Apoptosis in Reverse Polarization of Invasive Micropapillary Carcinoma of the Breast

Arai

Iwasaki

Tsuchiya

et al. 2020

Case Reports in Pathology

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Invasive micropapillary carcinoma (IMPC) is characterized by pseudopapillary tumor-cell clusters with a reverse polarity (RP) floating in lacunar spaces, with aggressive biological characteristics. The RP prevention is considered to inhibit IMPC, but its pathogenic mechanisms remain unclear. Annexin A2 (ANX A2), a cell-polarity protein, is known to be involved in lumenogenesis. ANX A2 expression is immunohistochemically examined, as well as both epithelial membrane antigen (EMA) and mucin-1 glycoprotein (MUC-1), the gold-standard markers for luminal differentiation, in the background tumor components of a case of IMPC. The following findings were noticed: (1) Apoptosis was scattered with peripheral apoptotic vacuolar change; (2) EMA and MUC-1 expressions were found, rimming the peripheral apoptotic vacuoles (including the contact surface with neighboring tumor cells), and these positions corresponded to the ones with a distinct ANX A2 positivity; and (3) partially detached tumor cells showed distinct positivity of three proteins at the stroma-facing surface, which is consistent with a RP. Taken together, frequent apoptosis in tumor cells with membranous accumulation of ANX A2 is considered to be indispensable for the reverse polarization of IMPC, and that secondary necrosis following apoptosis induces the cell-polarity disorder and creates detached tumor cells with a RP.

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“…The establishment, characterization, and staining protocol of S100A10 antibody have been previously described [ 22 , 23 ]. The characterization and staining protocol of ANX A2 antibody have been described elsewhere [ 22 , 24 ]. In immunostaining for pan-CK, the mouse monoclonal antibody multi-cytokeratin (cocktail of two clones, AE1/AE3, Leica Microsystems, Newcastle Upon Tyne, Tyne and Wear, UK) was used at 1:200 dilution, after a 5-min pretreatment with 0.4 mg/mL proteinase K (Dako, Glostrup, Denmark).…”

Section: Case Presentationmentioning

confidence: 99%

Membranous S100A10 involvement in the tumor budding of colorectal cancer during oncogenesis: report of two cases with immunohistochemical analysis

et al. 2020

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Background Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial-mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Case presentation In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, giving rise to TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders. Conclusions During oncogenesis, membranous S100A10 has the potential to be related to TB of CRC. This may be due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.

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Annexin A2 Expression in Aerogenous Metastasis of Pulmonary Invasive Mucinous Adenocarcinoma: A Case Report including Immunohistochemical Analysis

Cited by 4 publications

References 27 publications

Annexin A2 Expression in the Aerogenous Spread of Pulmonary Invasive Mucinous Adenocarcinoma with Gastric Lineage

Annexin A2 Expression in the Aerogenous Spread of Pulmonary Invasive Mucinous Adenocarcinoma with Gastric Lineage

Involvement of Annexin A2 Expression and Apoptosis in Reverse Polarization of Invasive Micropapillary Carcinoma of the Breast

Membranous S100A10 involvement in the tumor budding of colorectal cancer during oncogenesis: report of two cases with immunohistochemical analysis

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