The basement membrane is considered to act as a barrier which hinders cancer cells from invading the surrounding stroma. In order to assess changes in essential components during neoplasia in the lung, we immunohistochemically studied distribution patterns of laminins α α α α3 and α α α α5 in 40 adenocarcinomas and 8 squamous cell carcinomas. The α α α α5 chain was generally preserved at the periphery, frequently disrupted in foci with alveolar collapse and absent in foci of fibroblastic proliferation within adenocarcinomas. Fragmentation and absence of laminin α α α α3 chain were more prominent than for α α α α5 chain. Laminin α α α α3 chain was partially fragmented or absent in peripheral areas of adenocarcinomas, being significantly different from α α α α5 chain. Non-small cell lung cancers with reduced α α α α5 chain showed a tendency for greater lymph node metastasis. In cultured normal air way epithelial cells, both laminin α α α α3 and α α α α5 chains were found to be expressed by northern analysis. Eleven of the twelve cultured lung cancer cell lines did not express α α α α3 chain and expression of α α α α5 chain was reduced in three. Quantitative RT-PCR analysis also demonstrated expression of laminin α α α α3 chain in adenocarcinoma tissues to be significantly lower than in normal lung tissues.These results suggest that expression of laminin α α α α chains is often reduced in lung cancer cells and this might contribute to basement membrane fragmentation and subsequent proliferation of stromal elements, as well as play some role in the process of cancer cell invasion.Key words: Lung -Cancer -Basement membrane -LamininIn neoplastic tissue, the basement membrane is considered to act as a barrier which hinders the cancer cells from invading the surrounding stroma.1) With adenocarcinomas of the lung, disruption of basement membrane and linkage with lymph node metastasis and a poor prognosis have been reported. [2][3][4][5] Because the epithelial basement membrane is known to be renewed through turnover over several weeks, 6) two putative processes leading to fragmentation can be hypothesized. One is increased degradation of basement membrane by proteinases, such as collagenase, secreted by the cancer cells themselves or by the surrounding stromal cells. 3,7,8) The other possibility is that a reduced capacity of cancer cells to synthesize basement membrane components might exert an influence.The epithelial basement membrane is considered to be formed from materials secreted by both epithelial and stromal cells.9-11) Laminins, one of the major components of the basement membrane, are heterotrimeric glycoproteins composed of one large α chain and two smaller β and γ chains.12) In the process of heterotrimer assembly in the endoplasmic reticulum, laminin α chains are considered to be limiting factors. [13][14][15] There are 5 isoforms of laminin α chains and α2, 3, 4, 5 are considered to be expressed in the mouse and human lung (we could not detect the expression of α2 chain immunohistochemically in this study)...
Granulomatosis with Polyangiitis (GPA) is a necrotizing vacuities affecting medium and small sized blood vessels and produces necrotizing granulomas often involving the upper and lower respiratory tract. GPA can present as tumor like masses in the breast and kidney [1]. However, an association between GPA and renal cell cancer has also been reported [2]. We report a GPA patient who presented with abdominal pain and was found to have a renal and paraspinal mass which were biopsied revealing two distinct pathologic entities. A 74 year old Caucasian male was diagnosed with PR3 ANCA positive GPA in 2010 when he presented with acute kidney injury and had biopsy proven pauci-immune glomerulonephritis. He achieved disease remission with remission induction therapy with glucocorticoids and Cyclophosphamide. He experienced a renal relapse in 2013 and achieved disease remission with glucocorticoids and rituximab. He presented in March 2016 with abdominal pain and was found to have a right renal mass and a paraspinal mass. Ultrasound guided biopsy of the renal mass revealed clear cell renal cell carcinoma. Four days after the biopsy, he was admitted with fatigue, night sweats and arthralgias. Laboratory data were notable for a rise in serum creatinine, proteinuria and hematuria. His inflammatory markers were elevated and his PR3 ANCA titer had increased by two fold. His B cells showed reconstitution. He underwent biopsy of his paraspinal mass which revealed necrotizing granuloma with no evidence of infection or malignancy. He was treated with glucocorticoids and rituximab. His serum creatinine improved and his hematuria and proteinuria resolved. His inflammatory markers normalized and his PR3 ANCA titer became negative. His repeat CT scan revealed improvement in the size of the paraspinal mass (Figure 1 and 2). He subsequently underwent cryoablation of his right renal mass in October 2016.
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