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Prognostic value of desmoplastic reaction and lymphocytic infiltration in the management of breast cancer.

OBJECTIVE: To ascertain whether the prognostic value of desmoplastic reaction and lymphocytic infiltration are a good prognostic index to estimate survival in breast cancer patients. METHODS: From 1987 to 1994, the authors have evaluated the prognostic value of desmoplastic reaction and lymphocytic infiltration related to rode state in 34 patients with breast cancer. For statistical analysis and comparison of means the "t"-test was used. The significance level was 0.01. RESULTS: The group of patients with abundant desmoplastic reaction shows an overall survival rate lower than the group with poor desmoplastic reaction (p < 0.01) and the survival of the group with abundant desmoplastic reaction was related to lymphnodal status. CONCLUSIONS: Many prognostic factors have been shown during these years, some connected to patient, some connected to neoplasm and others connected to the treatment. Recently many other prognostic factors have been recognized, among which the possible prognostic role of desmoplasia has been carefully valued. Certainly, today the prognostic value of desmoplastic reaction and lymphocytic infiltration cannot take the place of usual prognostic factors in the evaluation of breast cancer patient yet the desmoplastic reaction is a good prognostic index to estimate the survival in these patients.

Adult↗

Multiphasic helical CT criteria for differentiation of recurrent neoplasm and desmoplastic reaction after laparoscopic resection of renal mass lesions.

BACKGROUND AND PURPOSE: Differentiation of recurrent neoplasm and desmoplastic reaction following laparoscopic resection of renal mass lesions poses a problem. The usefulness of multiphasic helical CT-generated criteria based on enhancement and morphologic characteristics was investigated. PATIENTS AND METHODS: The findings in 5 female and 12 male patients aged 29 to 68 years having renal-cell carcinoma (11-38 mm; N = 15) or solitary angiomyolipomas (N = 2) treated by laparoscopic resection (N = 15) or open segmental surgery (N = 2) were analyzed. Multiphasic helical CT was performed in the preenhancement, arterial corticomedullary, parenchymal, and excretory phases generating 2.5- to 7-mm slices. RESULTS: Both recurrent neoplasms showed median postcontrast enhancement of 119 HU in the arterial corticomedullary phase; the median enhancement of desmoplastic masses was 48 HU. In the parenchymal and excretory phase, recurrent neoplasms showed progressive loss of enhancement, whereas desmoplastic lesions sustained enhancement at about the same level. Recurrent neoplasms presented a defined mass with characteristic spiculation, whereas desmoplastic reaction was characterized by an ill-defined mass with spidery projections extending to abutting fat and residual fascial planes. On 2- to 3-month follow-up scans, recurrent neoplasms showed progressive increases in size and desmoplastic reaction a sharp decrease. CONCLUSION: Enhancement of the mass at the operative site on arterial corticomedullary-phase CT to >90 HU strongly suggests recurrent renal-cell carcinoma, while progressive decrease in size on 1- to 3-month follow-up CT suggests a desmoplastic reaction.

Adult↗

Myofibroblasts are responsible for the desmoplastic reaction surrounding human pancreatic carcinomas.

BACKGROUND: The cell type responsible for the desmoplastic reaction surrounding human pancreatic carcinoma is unknown. Hepatic stellate cells, which activate to a myofibroblast-like form, are responsible for collagen deposition in cirrhosis and around hepatocellular carcinomas. Recently, pancreatic stellate cells have been described and implicated in the fibrosis of chronic pancreatitis. We sought to determine whether these cells are responsible for the scirrhous reaction surrounding pancreatic adenocarcinomas. METHODS: Archival formalin-fixed, paraffin-embedded pancreatic tissues from 10 patients undergoing pancreaticoduodenectomy for ductal adenocarcinoma and from 2 patients with pancreatic islet cell tumors were examined immunohistochemically for alpha-smooth muscle actin (alpha-SMA), smooth muscle myosin heavy chain (SMMHC), procollagen I, collagen IV, and endothelial cell markers, von Willebrand factor and cluster of differentiation 31. RESULTS: In non-neoplastic areas, staining for alpha-SMA and SMMHC was confined to interlobular septal regions. In contrast, the desmoplastic reaction surrounding all 10 pancreatic adenocarcinoma specimens displayed intense interstitial staining for alpha-SMA, SMMHC, and collagen IV but no staining for von Willebrand factor and cluster of differentiation 31. Procollagen I staining localized intracellularly to fibroblast-shaped cells within this alpha-SMA/SMMHC-positive scirrhous region. Islet cell tumors demonstrated an increase in alpha-SMA staining, although this was not as marked as in ductal adenocarcinomas. CONCLUSIONS: A massive increase in myofibroblast activity, compatible with the activation of stellate cells, is associated with the deposition of collagen types I and IV in the desmoplastic reaction around pancreatic adenocarcinomas.

Actins↗

Tumor necrosis factor alpha and interleukin 11 secreted by malignant breast epithelial cells inhibit adipocyte differentiation by selectively down-regulating CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma: mechanism of desmoplastic reaction.

The dense layer of fibroblasts that accumulate around malignant breast epithelial cells (i.e., desmoplastic reaction) arises from the breast adipose tissue and provides structural and biochemical support for breast cancer. We report herein a number of epithelial-stromal interactions responsible for desmoplastic reaction in breast cancer using cultured 3T3-L1 murine fibroblasts and human adipose fibroblasts, which can be activated with a mixture of hormones to differentiate to mature adipocytes. Adipocyte differentiation was inhibited by coculturing fibroblasts with various breast cancer cell lines (T47D, MCF-7, SSC202, SSC78, and SSC30) completely or by breast cancer cell conditioned media in a dose-dependent manner; on the other hand, adipocyte differentiation was not inhibited by coculturing with normal human primary mammary epithelial cell conditioned medium. This tumor effect was eliminated using neutralizing antibodies against tumor necrosis factor (TNF)-alpha or interleukin (IL)-11. TNF-alpha and IL-11 levels were 2.5-3 times higher in T47D conditioned medium compared with control medium, and TNF-alpha transcripts were detectable in T47D but not in 3T3-L1 cells in culture, indicating that the malignant epithelial cell is the major site of cytokine production. This was confirmed in vivo in mastectomy specimens, where immunoreactive TNF-alpha and IL-11 were readily detectable in malignant epithelial cells but not in the majority of the surrounding fibroblasts. Adipocyte differentiation is mediated by the expression of a cascade of adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBP)beta, C/EBPdelta, peroxisome proliferator-activated receptor (PPAR)gamma and C/EBPalpha. C/EBPalpha and PPARgamma are essential for this process. We demonstrated by Northern analysis that exposure of activated 3T3-L1 cells to T47D cell conditioned medium strikingly decreased the levels of PPARgamma and C/EBPalpha transcripts and increased the levels of C/EBPbeta and C/EBPdelta transcripts. In these 3T3-L1 cells, inhibition of differentiation was also confirmed by markedly suppressed levels of aP2 mRNA, which is an adipocyte-specific gene. These in vitro observations were confirmed in sections of human malignant breast tumors, where immunoreactive C/EBPalpha was readily detectable in adipose flbroblasts distant to the tumor but not in intratumoral fibroblasts. Treatment of 3T3-L1 cells with T47D cell conditioned medium or TNF-alpha changed neither the numbers of cells in G0-G1, S, and G2 phases nor the rate of [3H]thymidine incorporation, thus ruling out a proliferative effect of malignant cells on the surrounding fibroblasts. In summary, desmoplastic reaction primarily occurs via the action of cytokines (TNF-alpha and IL-11) secreted by the malignant epithelial cells to inhibit differentiation of adipose fibroblasts to mature adipocytes. This tumor-induced block in adipocyte differentiation is mediated by the selective inhibition of expression of the essential adipogenic transcription factors, i.e., PPARgamma and C/EBPalpha.

3T3 Cells↗

Desmoplastic reaction of gastric carcinoma: a light- and electron-microscopic immunohistochemical analysis using collagen type-specific antibodies.

The desmoplastic reaction in ten cases of gastric carcinoma was investigated light and electron immunohistochemically by using monospecific antibodies to collagen types. In addition to type I and III collagens, type V collagen was constantly recognized in the fibrous stroma, increasingly of the scirrhous carcinoma. Type IV collagen delineated the basement membranes of carcinoma nests linearly with occasional discontinuity, whereas in the scirrhous carcinoma, it was present along the thick bundles of collagenous fibers. Immunoelectron microscopic studies revealed that type I and III collagens were distributed on the collagen fibers, and type V collagen was stained in the margin of these fibers. These antibodies also reacted in the rough endoplasmic reticulum of fibroblasts or myofibroblasts in a few cases. Type IV collagen was localized in the periphery of smooth muscle cells, endothelial cells of collapsed capillaries, and myofibroblasts scattered in the stroma of scirrhous carcinoma. Carcinoma cells were not reactive with any antibodies examined. These findings suggest that type V collagen, as well as type I and III collagens, is involved in the formation of desmoplastic stroma, and that these collagens are reactively synthesized by fibroblasts and myofibroblasts in some interaction with invading carcinoma cells.

Animals↗

Desmoplastic reaction influences pancreatic cancer growth behavior.

Connective tissue growth factor (CTGF), which is regulated by transforming growth factor-ss (TGFss), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46-fold increase in CTGF mRNA expression ( p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFss-induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation ( p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) ( p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFss, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.

Adenocarcinoma↗

Correlation between MRI and histopathologic findings in stage I cervical carcinomas: influence of stromal desmoplastic reaction.

Although the effectiveness of magnetic resonance imaging (MRI) in depicting cervical carcinoma has been reported, whether MRI can detect early-stage or stage IB "occult"-type cervical carcinoma remained undetermined. We examined the correlation between MRI and pathologic findings in 38 stage I (IB 28 cases, IA 10 cases) cervical carcinoma patients, with special reference to the influence of desmoplastic stromal reaction around the tumor. The results demonstrated that the tumor was detected by MRI in none of stage IA patients but in 21 (75%) stage IB patients. The image was clearly demonstrated in 15 of 18 (83%) tumors of more than 2 cm in diameter and in 6 of 10 (60%) tumors of 2 cm or less. The tumor image was evident in 21 of 22 (95%) tumors with prominent (>200 micron) stromal reaction but in none of 6 tumors with minimal (</= 200 micron) stromal reaction. These findings suggest that MRI is not useful for the detection of stage IA tumors. In stage IB tumors, however, the stromal reaction rather than the size of the tumor may influence the tumor's image in MRI.

Adenocarcinoma↗

Pleomorphic xanthoastrocytoma with desmoplastic reaction: angiomatous variant. Report of two cases.

Two cases of cerebral pleomorphic xanthoastrocytomas (PXA-s) with prominent vascularity and desmoplastic changes occurring in young subjects are presented. The tumors displayed the marked pleomorphism characteristic of PXA-s and had variable cellularity. The cytoplasm of many tumor cells contained an abundance of lipid droplets. Most tumor cells were positive for glial fibrillary acidic protein. The unusual feature about these tumors was the presence of very large numbers of tiny blood vessels with variable thickness of their walls. In many areas the small vessels and the neoplastic astrocytes were in close proximity to each other, with capillaries adjacent to or protruding into tumor cell cytoplasm, reminiscent of the pattern seen in highly vascularized or "angiomatous" meningiomas. In other areas extensive fibrosis was seen. We feel that the latter, as in the cases of comparably vascular meningiomas, had its origin in congelation and secondary organization of plasma proteins that have exuded through leaky walls of newly formed blood vessels. These are the first reported cases of PXA with an angiogliomatous pattern.

Adult↗

Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells.

OBJECTIVES: Pancreatic cancer has a very poor prognosis, largely due to its propensity for early local and distant spread. Histopathologically, most pancreatic cancers are characterized by a prominent stromal/fibrous reaction in and around tumor tissue. The aims of this study were to determine whether (1) the cells responsible for the formation of the stromal reaction in human pancreatic cancers are activated pancreatic stellate cells (PSCs) and (2) an interaction exists between pancreatic cancer cells and PSCs that may facilitate local and distant invasion of tumor. METHODS: Serial sections of human pancreatic cancer tissue were stained for desmin and glial fibrillary acidic protein (stellate cell selective markers) and alpha-smooth muscle actin (alphaSMA), a marker of activated PSC activation, by immunohistochemistry, and for collagen using Sirius Red. Correlation between the extent of positive staining for collagen and alphaSMA was assessed by morphometry. The cellular source of collagen in stromal areas was identified using dual staining methodology, ie, immunostaining for alphaSMA and in situ hybridization for procollagen alpha1I mRNA. The possible interaction between pancreatic cancer cells and PSCs was assessed in vitro by exposing cultured rat PSCs to control medium or conditioned medium from 2 pancreatic cancer cell lines (PANC-1 and MiaPaCa-2) for 24 hours. PSC activation was assessed by cell proliferation and alphaSMA expression. RESULTS: Stromal areas of human pancreatic cancer stained strongly positive for the stellate cell selective markers desmin and GFAP (indicating the presence of PSCs), for alphaSMA (suggesting that the PSCs were in their activated state) and for collagen. Morphometric analysis demonstrated a close correlation (r = 0.77; P < 0.04; 8 paired sections) between the extent of PSC activation and collagen deposition. Procollagen mRNA expression was localized to alphaSMA-positive cells in stromal areas indicating that activated PSCs were the predominant source of collagen in stromal areas. Exposure of PSCs to pancreatic cancer cell secretions in vitro resulted in PSC activation as indicated by significantly increased cell proliferation and alphaSMA expression. CONCLUSIONS: Activated PSCs are present in the stromal reaction in pancreatic cancers and are responsible for the production of stromal collagen. PSC function is influenced by pancreatic cancer cells. Interactions between tumor cells and stromal cells (PSCs) may play an important role in the pathobiology of pancreatic cancer.

Actins↗

Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma.

BACKGROUND: Several studies have shown the prognostic value of desmoplasia for lung adenocarcinomas. The authors evaluated the density and extent of desmoplasia by modifying the scar grade, as well as the prognostic impact on patient survival. METHODS: Modified scar grade was defined as follows: Grade 1, no desmoplasia; Grade 2, sparse desmoplastic reaction; Grade 3, dense desmoplastic reaction with diameter of 10 mm or less; Grade 4, dense desmoplastic reaction with diameter exceeding 10 mm. In addition, the prognostic impact of conventional histologic factors and modified scar grade was analyzed in 239 cases of small peripheral lung adenocarcinoma (maximum dimension, </= 30 mm) for which long-term follow-up data were available. RESULTS: The 5 and 10-year survival rates according to the modified scar grade were 100% and 100% for Grade 1 lung adenocarcinoma (n = 29); 91.7% and 83.7% for Grade 2 (n = 61); 67.6% and 52.7% for Grade 3 (n = 78); and 50.0% and 37.5% for Grade 4 (n = 71), respectively. A significant difference in patient survival was found between Grade 1 or 2 versus Grade 3 or 4 (P < 0.0001, by log rank test). Multivariate analysis showed that modified scar grade was an independent prognostic factor (P = 0.0176), as were pathologic stage (P = 0.0293), lymph node metastasis (P = 0.0191), lymphatic permeation (P = 0.0022), and pleural involvement (P = 0.0452). Modified scar grade also had a significant impact on survival in various subsets of patients, including those with pathologic Stage IA disease, patients with tumors of diameter 20 mm or less, or patients with mixed subtype tumors with a bronchioloalveolar component. CONCLUSIONS: Modified scar grade is a useful prognostic factor in patients with small lung adenocarcinomas. Tumors with a sparse fibroblastic reaction (modified scar Grade 2) may represent early invasive cancers or invasive cancers with low malignant potential, which should be distinguished from frankly invasive cancers (modified scar Grade 3 or 4).

Adenocarcinoma↗

Cytokeratin-negative desmoplastic small round cell tumor: a report of two cases emphasizing the utility of reverse transcriptase-polymerase chain reaction.

Desmoplastic small round cell tumor (DSRCT) is a unique, highly aggressive neoplasm that chiefly affects male adolescents and young adults. This tumor is characterized by nests of small undifferentiated cells that show immunohistochemical evidence of epithelial, mesenchymal, and neural differentiation. We report two cases of DSRCT that lacked immunohistochemical evidence of epithelial differentiation, but were found to have the fusion transcripts characteristic of this tumor. Both patients (a 41-year-old male and a 31-year-old female) presented with large intra-abdominal masses. After diagnostic biopsy, both were treated with multi-agent chemotherapy. One patient expired 18 days after diagnosis, and the other is currently alive 28 months later. Histologically, both tumors had the characteristic features of DSRCT and were composed of small round cells with hyperchromatic nuclei and scanty cytoplasm. In one of the cases, perinuclear intracytoplasmic hyaline inclusions were seen. Immunohistochemically, neither case expressed any of the epithelial markers tested, including AE1/AE3, CAM 5.2 and EMA. Both tumors were diffusely immunoreactive for desmin with a prominent globoid "dot-like" pattern of staining in one case. Both tumors stained for vimentin, neuron specific enolase, and synaptophysin, but were negative for CD99, muscle-specific actin, and myogenin. Reverse transcriptase-polymerase chain reaction revealed EWS-WT1 fusion transcripts characteristic of this neoplasm. In conclusion, we describe two cases of DSRCT that lacked immunohistochemical evidence of epithelial differentiation but had histologic and other immunohistochemical features which suggested this diagnosis. The ability to confirm the diagnosis of this rare tumor using molecular genetic techniques is particularly useful in those cases with unusual histologic or immunophenotypic features.

Abdominal Neoplasms↗

Juxtatumoral desmoplastic stromal reaction is associated with high tumor cell dissociation in squamous cell carcinomas of the uterine cervix.

There are different types of tumoral growth patterns invading host tissue. During tumor infiltration, cancer cells not only destroy the pre-existing extracellular matrix, but usually induce new matrix formation by activating the peritumoral stromal cells; that is, desmoplastic stromal reaction (DSR) at the front of invasion (juxtatumoral stroma). This study evaluates the association between different types of invasion and DSR. Eighty-eight squamous cell carcinomas (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] stage IB to IV) were evaluated histologically for different patterns of invasion (PI) using a 3-level scoring system (pushing, finger-like, and spray-like). Desmoplastic stromal reaction was scored from none to weak, moderate, or strong. The pattern of invasion and DSR were compared with patients' age, FIGO stage, clinical tumor size, tumor grade, and the presence of lymphovascular space involvement. Finger-like PI was the most common (72.7%), followed by the spray-like PI (27.3%), whereas pushing PI was not seen. Of the tumors, 23.9% showed no DSR; 51.1%, weak; 14.8%, moderate; and 10.2%, strong DSR. Tumors with spray-like PI showed a significantly stronger desmoplastic reaction compared with the finger-like PI (P < .0001) and were significantly associated with poor tumor cell differentiation (P = .018). Moderate or strong DSR was associated with G2 and G3 carcinomas (P = .027). No correlation was seen neither for PI and DSR to lymphovascular space involvement, FIGO stage, and tumor size. The intensity of DSR, as understood in the context of a remodeling of the juxtatumoral stroma to the infiltrative tumor growth, might be indicative of a highly dissociative tumor growth and is correlated to poorly differentiated tumors.

Adult↗

MUC1 and cathepsin D expression in early colorectal carcinoma showing V type pit pattern.

The relation between MUC1, cathepsin D expression, and histologic features in early colorectal carcinomas (CRCs) with V type pit pattern was examined in 78 patients. We classified V type pit pattern into two grades (VA, VN) and we subclassified the VN type pit pattern into three subtypes (Grade A, B, and C) according to the degree of appearance of VN type pit pattern. At the tumor surface, the status of desmoplastic reaction and pit disorder or destruction were subclassified histologically into three grades (-, +, ++). MUC1 and cathepsin D expression were examined immunohistochemically at a superficial level and at the deepest part of the tumor invasion. MUC1 expression showed a significant correlation with high grade carcinoma, desmoplastic reaction (+) levels in VA type pit pattern (P<0.05), and high grade carcinoma, sm2 and sm3 lesions, desmoplastic reaction (+) and (++) levels, pit disorder or destruction (+) and (++) levels in VN type pit pattern (P<0.05). Cathepsin D expression had a significant correlation with m and sm1 lesions and desmoplastic reaction (-) levels in VN type pit pattern (P<0.05). In VA type pit pattern, a significant correlation between cathepsin D expression and histologic findings was absent. The incidence of MUC1 expression in VN.Grade B and C type pit pattern was significantly higher than that in VA and VN.Grade A type pit pattern (P<0.05). The incidence of cathepsin D expression in VA, VN.Grade A and B type pit pattern was significantly higher than that in VN.Grade C type pit pattern (P<0.05). MUC1 expression (+) or (++) levels at the deepest part of a tumor was identical to that (+) or (++) levels at the superficial part except for one case. Cathepsin D expression at the deepest part of a tumor differed from that at the superficial part. Desmoplastic reaction may be related to MUC1 and cathepsin D expression; however, pit disorder or destruction may be related to only MUC1 expression in V type pit pattern. MUC1 expression at the superficial part of a tumor may be related to expression at the deepest part; however, cathepsin D expression at the superficial part may not be related to expression at the deepest part in submucosal CRCs with V type lesions.

Cathepsin D↗

[Prognostic significance of desmoplasia in breast carcinoma. A preliminary clinical study].

This study carried on 61 patients with breast cancer confirmed the biological assumption of a higher malignancy in tumors with strong desmoplastic reaction. Patients in stage II A, II B and III presenting a marked desmoplastic reaction have a shorter DFS (disease free survival). Therefore, desmoplastic reaction may be considered a marker of local malignancy and metastatic process.

Adult↗

Desmoplastic stromal reaction in medullary thyroid cancer-an intraoperative "marker" for lymph node metastases.

BACKGROUND: Medullary thyroid cancer (MTC) disseminates early to lymph nodes (LN). There is no pre- or intraoperative marker to exclude LN involvement and thereby avoid lateral neck dissection in LN-negative patients. MATERIALS AND METHODS: This study was intended to verify the observation that patients with MTC lacking desmoplastic stromal reaction (DSR) never have LN metastases. In 120 patients undergoing primary operation for sporadic MTC the prognostic value of DSR with respect to LN involvement was evaluated. RESULTS: Thirty-two (27%) of 120 tumors were DSR negative, and 88 (73%) were DSR positive. All 32 (100%) DSR-negative tumors were LN negative (N0), and all patients were biochemically cured. Of 88 DSR-positive tumors, 57 (65%) were staged N0, and 31 (36%) were staged N1(LN positive; Fisher's exact test: P = 0.0001). In a comparison of the LN involvement to the DSR characteristics, 32 (36%) of the 89 N0 patients and none of the 31 N1 patients were DSR negative. The sensitivity of DSR in predicting N0 is 38% (95% confidence interval: CI 95% = 27 %-55%), the specificity is 100% (CI 95% = 88%-100%). The sensitivity and specificity for the parameter DSR to differentiate between N0 or N1 were 100% and 36%, respectively. CONCLUSIONS: The desmoplastic stromal reaction appears to be an excellent intraoperative marker to predict LN involvement with a high specificity but low sensitivity. We therefore propose to avoid initial lateral neck dissection in MTC patients without DSR.

Adult↗

Schirrous invasive ductal carcinoma of the breast overexpress p53 oncoprotein.

CONTEXT: Breast cancer is the most important neoplasm in adult women, and its worldwide incidence is growing. The tumoral stroma is very important for modulating the growth and invasion of the tumor itself. The relationship between these two components is not completely understood. Schirrous carcinoma is a variant of ductal invasive carcinoma in which the stroma is very desmoplastic, and the importance of this finding still a motive for debate in the literature. OBJECTIVE: To compare the desmoplastic reactions against biological markers, such as estrogen and progesterone receptors, oncoprotein c-erbB-2 and oncoprotein p53, with the objective of studying the relationship between the tumoral stroma and epithelial cancer cells. TYPE OF STUDY: Retrospective study. SETTING: Cancer Hospital A C Camargo and Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. SAMPLE: 107 adult women operated because of ductal invasive carcinoma. The cases were separated into 4 groups according to the desmoplastic reaction - less than 15 per cent, between 15-50 per cent, 51-85 per cent, and more than 85 per cent fibrosis. The grade of fibrosis was determined by picrus-sirius staining and quantified by using a microscope with a stereo-imaging grid. Immunohistochemical methods were used to determine the expression of the hormonal receptors and c-erbB-2/p53 oncoprotein. MAIN MEASUREMENTS: Extent of desmoplastic reaction versus expression of estrogen and progesterone receptors, oncoprotein c-erbB-2, and oncoprotein p53. RESULTS: The results showed that schirrous carcinoma expresses oncoprotein p53 more frequently than other carcinomas with less extensive desmoplastic reaction. There were no differences between the grade of fibrosis and the other biological markers. CONCLUSION: The intense stromal reaction in invasive ductal carcinoma may modulate the expression of p53. Further investigations should be made with the aim of understanding how this expression determines the proliferative activity in schirrous carcinoma, and whether this overexpression is secondary to mutation of the p53 gene or due to modulation of other molecules of the stroma.

Adult↗