Journal of Pathology and Translational Medicine

Original Articles

An Immunohistochemical and Polarizing Microscopic Study of the Tumor Microenvironment in Varying Grades of Oral Squamous Cell Carcinoma: Aeman Khalid, Safia Siddiqui, Bharadwaj Bordoloi, Nafis Faizi, Fahad Samadi, Noora Saeed; J Pathol Transl Med. 2018;52(5):314-322. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.17

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Background
Invasion of epithelial cells into the connective tissue brings about massive morphological and architectural changes in the underlying stroma. Myofibroblasts reorganize the stroma to facilitate the movement of tumor cells leading to metastasis. The aim of this study was to determine the number and pattern of distribution of myofibroblasts and the qualitative and quantitative change that they cause in the collagen present in the stroma in various grades of oral squamous cell carcinoma (OSCC).
Methods
The study was divided into two groups with group I (test group, 65 cases) consisting of 29 cases of well-differentiated squamous cell carcinoma, 25 moderately differentiated SCC, and 11 poorly differentiated SCC, and group II (control group) consisting of 11 cases of normal mucosa. Sections from each sample were stained with anti–α-smooth muscle actin (α-SMA) antibodies, hematoxylin and eosin, and Picrosirius red. Several additional sections from each grade of OSCC were stained with Masson’s trichrome to observe the changes in collagen. For the statistical analysis, Fisher’s exact test, Tukey’s post hoc honest significant difference test, ANOVA, and the chi-square test were used, and p < .05 was considered statistically significant.
Results
As the tumor stage progressed, an increase in the intensity α-SMA expression was seen, and the network pattern dominated in more dedifferentiated carcinomas. The collagen fibers became thin, loosely packed, and haphazardly aligned with progressing cancer. Additionally, the mean area fraction decreased, and the fibers attained a greenish yellow hue and a weak birefringence when observed using polarizing light microscopy.
Conclusions
Myofibroblasts bring about numerous changes in collagen. As cancer progresses, there isincrease in pathological collagen,which enhances the movement of cells within the stroma.

Citations

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Multifractal Alterations in Oral Sub-Epithelial Connective Tissue During Progression of Pre-Cancer and Cancer
Debaleena Nawn, Sawon Pratiher, Subhankar Chattoraj, Debjani Chakraborty, Mousumi Pal, Ranjan Rashmi Paul, Srimonti Dutta, Jyotirmoy Chatterjee
IEEE Journal of Biomedical and Health Informatics.2021; 25(1): 152. CrossRef

The Expression of Transforming Growth Factor-beta1 and alpha-Smooth Muscle Actin is Increased in the Human Myxomatous Valve.: Jeong Hwan Park, Ho Joong Youn, Jung Sook Yoon, Chul Soo Park, Soo Sung Oh, Woo Baek Chung, Jong Won Chung, Yun Seok Choi, Dong Hyun Lee, Yong Seog Oh, Wook Sung Chung, Soon Jo Hong, Youn Soo Lee, Sung Bo Sim, Sun Hee Lee; Korean J Pathol. 2009;43(2):152-156.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.152

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Abstract PDF

BACKGROUND
In vitro experimental studies have reported that transforming growth factor-beta1 (TGF-beta1) stimulates the production of alpha-smooth muscle actin (alpha-SMA) in porcine valves. However, the relation between TGF-beta1 and alpha-SMA in myxomatous valves has not been elucidated.
METHODS
We classified 27 subjects into two groups: 1) myxomatous group (M:F=11:12, mean age=55+/-15 years) and 2) rheumatic group (M:F=3:1, mean age=41+/-17 years) according to preoperative echocardiographic and postoperative histologic findings. Twenty-seven valve specimens from the patients who underwent valve replacement were obtained. Tissue samples were analyzed by immunohistochemistry for TGF-beta1 and alpha-SMA. The positively stained areas were measured using an image analysis program (Image Pro-Plus 4.5), and then the TGF-beta1 volume fraction (TGF-VF) and alpha-SMA volume fraction (alpha-SMA-VF) were calculated.
RESULTS
TGF-VF in myxomatous valves was higher than in rheumatic valves (2,759+/-2,294 vs 864+/-276, p=0.04). alpha-SMA-VF in myxomatous valves was higher than in rheumatic valves (4,122+/-2,275 vs 2,421+/-844, p=0.002). There was a significant correlation between TGF-beta1 and alpha-SMA in myxomatous valves (r=0.38, p=0.04). There was no significant correlation between TGF-beta1 and alpha-SMA in rheumatic valves (r=-0.50, p=0.67).
CONCLUSIONS
TGF-beta1 and alpha-SMA may be related to the pathogenesis of myxomatous valves. The activation of TGF-beta1 might increase the expression of alpha-SMA in human myxomatous valves.

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Apoptosis and abundance of Bcl-2 family and transforming growth factor β1 signaling proteins in canine myxomatous mitral valves
Sirilak Surachetpong, Treenate Jiranantasak, Anudep Rungsipipat, E. Christopher Orton
Journal of Veterinary Cardiology.2013; 15(3): 171. CrossRef
Pathology, protein expression and signaling in myxomatous mitral valve degeneration: Comparison of dogs and humans
Heike Aupperle, Sirilak Disatian
Journal of Veterinary Cardiology.2012; 14(1): 59. CrossRef

Expression of CD44 Splice Variants(v4/5 and v6), alpha-Smooth Muscle Actin, and nm23 Proteins in IB-IIB Uterine Cervical Cancer.: Hee Kyung Chang, Man Ha Huh, Dong Hee Kim, Un Dong Park; Korean J Pathol. 1997;31(6):546-556.

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Abstract PDF: We examined the expressions of CD44 splice variants (v4/5, v6), alpha-smooth muscle actin, nm23 to evaluate their roles as prognostic factors in 70 cases of uterine cervical carcinoma (stage IB to IIB) who were surgically treated from January 1989 to June 1990 with a clinical follow-up of a minimum of 5 years. The expression was examined by an immunohistochemical method using archival formalin fixed paraffin embedded tissue. In the 70 cases, 61 cases were squamous cell carcinoma and 9 cases were adenocarcinoma. CD44v4/5, CD44v6, alpha-smooth muscle actin, and nm23 were detected in 41.4%, 70%, 100%, and 74.3% of tumor samples, respectively. CD44 splice variants and nm23 showed membrane and cytoplasmic staining of tumor cells, respectively. The expression of alpha-smooth muscle actin showed cytoplasmic staining confined to stromal cells and was classified into three grades by the extent in stromal cells: with less than 10% of stromal cells; 32.9%, 10-50% of stromal cells; 40.0%, more than 50%; 27.1%. These expressions were not correlated with histologic types, lymph node involvement, recurrence, and grades of tumor infiltrating lymphocyte (TIL). But CD44v4/5 had significantly inverse correlation with TIL (p=0.049). The expression of CD44v4/5 was significantly correlated with that of CD44v6 (p=0.05), and that of alpha-smooth muscle actin was inversely correlated with that of nm23 (p=0.049). In conclusion, in FIGO IB-IIB uterine cervical carcinoma CD44 variants, nm23, and SMA show high prevalence, however, with little prognostic significance assessed by recurrence and lymph node metastasis.

Expression of Alpha Smooth Muscle Actin and Lysozyme in Various Glomerular Diseases.: Sun Hee Sung, Woon Sup Han; Korean J Pathol. 1998;32(1):51-57.

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Abstract PDF: The cells of glomerular mesangium is composed mostly of intrinsic contractile mesangial cells and a few macrophages. Injury to the mesangium is central to many glomerular diseases. This study was aimed to evaluate and compare the expressions of alpha-smooth muscle actin (ASMA) and lysozyme in the mesangium of various human glomerular diseases and also of according to the severity of their progressions. We performed immunohistochemical and transmission electromicroscopic examinations in 51 cases of renal biopsy including 5 normal kidneys. The results were as follows; (1) ASMA staining was negligible in normal glomeruli. (2) Increased ASMA staining was observed in the mesangium of glomeruli from all specimens of primary glomerular disease, regardless of their diagnosis. (3) The staining intensity of ASMA in mesangium was mild in minimal change disease and membranous glomerulonephritis, and strong in focal segmental glomerulosclerosis (FSGS), diffuse mesangial hypercellularity, membranoproliferative glomerulonephritis (MPGN), and IgA nephropathy (IgAN). (4) The staining intensity of ASMA have no correlation with mesangial immune deposits. (5) The staining intensity of ASMA in mesangium was inversely correlated with the disease progression in FSGS and IgAN. (6) Glomeruli showing global or segmental sclerosis invariably lacked ASMA. (7) Compared with ASMA, the mesangial cells with lysozyme expression were very rare, even though it was in proportion to ASMA staining. Interstitial ASMA expression was confined to fibrotic area in various glomerular diseases. In conclusion, the expression of ASMA and lysozyme in mesangium are increased in a variety of glomerular diseases, regardless of disease entity. Their intensity was in proportion to the mesangial cell proliferation. In progressive glomerulonephritis, such as IgAN and FSGS, the increased expression of ASMA was prominent in the early lesion, and decreased with the progression of the glomerular sclerosis.

Expression of Glomerular-Smooth Muscle Actin and Vimentin in Idiopathic Membranous Nephropathy as Prognostic Indicators.: Min Jin Lee, Ok Kyung Kim; Korean J Pathol. 2001;35(1):26-34.

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Abstract PDF: BACKGROUND
The natural history of idiopathic membranous nephropathy (IMN) is heterogeneous with some patients showing spontaneous remission while others show a progressive course leading to end-stage renal failure. We tried to assess quantitatively alpha-smooth muscle actin (alpha-SMA) and vimentin expression as markers to predict the outcome of membranous nephropathy.
METHODS
This study included 24 patients with biopsy proven IMN. We measured the volume of the positive area for alpha-SMA and vimentin within the glomeruli and compared the results with 5 patients in the normal control group. We evaluated glomerular alpha-SMA and vimentin expression in correlation with BUN and serum creatinine level at the time of diagnosis and after treatment.
RESULTS
Glomerular alpha-SMA and vimentin in IMN were higher than in the control group. Glomerular alpha-SMA was significantly higher in progressive IMN than in non-progressive IMN. The glomerular alpha-SMA was sifnificantly correlated with BUN and serum creatinine at last follow-up (p<0.05), but there was no statistically significant correlation at diagnosis. The glomerular vimentin was not different between progressive and non-progressive groups.
CONCLUSION
These data suggest that the expression of glomerular alpha-SMA may be a useful prognostic indicator and may be able to differentiate between patients with membranous nephropathy who respond well to treatment and those who continue to progress.

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components.: Mee Sook Roh, Jong Woo Choi, Hyoun Wook Lee, Hyuk Chan Kwon, Tae Ho Park, Phil Jo Choi, Chang Hun Lee, Bong Kwon Cheon; Korean J Pathol. 2005;39(3):158-163.

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Abstract PDF: BACKGROUND
Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas.
METHODS
Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive).
RESULTS
The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%).
CONCLUSIONS
The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

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