The disappearance of CD34-positive and alpha-smooth muscle actin-positive stromal cells associated with human intra-uterine and tubal pregnancies

In order to elucidate the change in alpha-smooth muscle actin (ASMA)-positive and CD34-positive stromal cells associated with pregnancy, we examined endometrial and Fallopian tube tissues from 40 patients including normal endometrium (n=10), intra-uterine pregnancy (n=10), normal Fallopian tube (n=10), and tubal pregnancy (n=10), using immunohistochemistry. In normal endometrium, only a few ASMA-positive cells were focally observed. Additionally, a wide range of CD34-positive stromal cell abundance was observed. In normal Fallopian tube mucosa, a small to moderate number of both ASMA-positive and CD34-positive stromal cells was observed. Neither ASMA-positive nor CD34-positive stromal cells were observed anywhere in the decidual stroma during both intra-uterine and tubal pregnancies. Likewise, a varying abundance of ASMA-positive cells but no CD34-positive stromal cells were observed at the fetal side during both intra-uterine and tubal pregnancies. In conclusion, the disappearance of CD34-positive and ASMA-positive stromal cells may be an indicator of decidualisation induced change in the stroma during both intra-uterine and tubal pregnancies. ASMA-positive stromal cells at the fetal side associated with pregnancy may play a role in the production of villous extracellular matrix or regulation of blood flow.     

The distribution and role of myofibroblasts and CD34-positive stromal cells in normal pancreas and various pancreatic lesions

To elucidate the distribution and role of myofibroblasts and CD34-positive stromal cells in various pancreatic lesions, we performed an immunohistochemical study using a streptoavidin-biotin immunoperoxidase technique. We selected 43 pancreatic lesions from 1 biopsied, 22 surgically resected and 12 autopsied specimens: acute pancreatitis (n=3), chronic non-obstructive pancreatitis (n=4), obstructive pancreatitis (n=7), islet cell tumor (n=4), serous cystadenoma (n=7), mucinous cystadenoma (n=6), and invasive ductal carcinoma (n=12). In normal pancreas, myofibroblasts and CD34-positive stromal cells were predominantly present in the peridcutal and periacinar areas, respectively. Both myofibroblasts and CD34-positive cells were observed in the stroma of chronic pancreatitis. In four islet cell tumors, myofibroblasts were present in the stroma of the tumor center, but no CD34-positive stromal cells were identified. Additionally, myofibroblasts and CD34-positive stromal cells were located in the inner layer and the outer layer of the capsule of three islet cell tumors, respectively. In nine of the thirteen cystadenomas, only myofibroblasts were recognized in the cyst wall. In the remaining four cystadenomas, a small number of CD34-positive cells were observed in the cyst wall. In 12 invasive ductal carcinomas, the stroma possessed a lot of myofibroblasts, but there were no or few CD34-positive stromal cells. In conclusion, it seems that the abundant amount of CD34-stromal cells in the main lesions is characteristic of chronic inflammatory lesions. Myofibroblasts and CD34-positive stromal cells may play a role in regulating the tumor growth in the capsule of islet cell tumors of the pancreas.     

The distribution of CD34-positive stromal cells and myofibroblasts in colorectal carcinoid tumors

In order to understand the stromal reaction associated with colorectal neoplasms, we examined specimens from 26 patients including normal colorectal tissues (n=15), carcinoid tumors (n=12), well differentiated adenocarcinomas (n=10), and poorly differentiated adenocarcinomas (n=4), using an immunohistochemical method. Myofibroblasts and CD34-positive stromal cells were distributed in the mucosa and in the area between the submucosal and subserosal layers, respectively. However, the distribution of these cells markedly changed with the invasion of neoplasms. Namely, myofibroblasts were abundant in the invasive stroma of all colorectal neoplasms. CD34-positive stromal cells were completely absent from the invasive stroma of colorectal cancers. On the other hand, CD34-positive stromal cells were absent from four out of five carcinoid tumor cases with lesions measuring less than 2 mm in size, but were present in all seven cases of carcinoid tumors measuring more than 2 mm. Double-immunostaining identified stromal cells expressing both ASMA and CD34 in several carcinoid tumor cases. Finally, no CD34-positive stromal cells were observed in the invasive stroma of colorectal cancers. However, the distribution of these cells in carcinoid tumors may depend on the lesion size. Namely, CD34-positive stromal cells existed between neoplastic nests in large-sized carcinoid tumors. Myofibroblasts in the stroma of colorectal neoplasms may originate from CD34-positive stromal cells.     

Variable Stromal Periductular Expression of CD34 and Smooth Muscle Actin (SMA) in Intraductal Carcinoma of the Breast

In breast carcinoma, the stromal loss of CD34 expression and acquisition of SMA myofibroblastic features may constitute a prerequisite for tumor invasiveness. However, this hypothesis remains controversial, with some authors describing the loss of CD34 fibrocytes in the absence of SMA myofibroblastic-like cells in the stroma of invasive carcinoma. Others have also described the disappearance of CD34 fibrocytes from in situ carcinoma. To clarify this issue, we compared the distribution of CD34 fibrocytes and SMA reactive myofibroblasts between stromal areas of tumor-free mammary tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). In addition to 28 IDC, 300 normal duct–lobular units and 600 ducts with DCIS (158 low-grade, 266 intermediate, and 176 high-grade) were scored. The relationships between staining patterns and different histological features (grade of DCIS and presence or absence of necrosis) were compared. Loss of CD34 expression and acquisition of SMA expression were more frequent in high-grade in situ lesions than in intermediate and low-grade lesions (p<0.001). When necrosis was found in association with grade 2 or 3 DCIS, the decrease in CD34 expression was higher than in lesions without necrosis and that independently of the grade of DCIS (p<0.05). Necrosis did not appear to play a significant role in the expression of SMA (p = 0.35). In all cases, the stroma of invasive carcinomas showed a complete loss of CD34 fibrocytes. Future research on both CD34 fibrocytes and mechanisms stromal changes are essential in the future and may potentially lead to new treatment approaches.     

Fine needle aspiration cytology of invasive cribriform carcinoma of the breast with osteoclastlike giant cells: a case report

BACKGROUND: Nonneoplastic osteoclastlike giant cells are occasionally associated with carcinoma of the breast, pancreatobiliary and gastrointestinal systems. In the breast, this uncommon stromal response is seen mainly in invasive carcinoma with low grade cytology, among which invasive cribriform carcinoma is the classic example. Details of the fine needle aspiration cytology of this phenomenon, especially in thin-layer preparations, have been described rarely. CASE: The fine needle aspiration cytology of an invasive cribriform carcinoma of the breast occurred in a 66-year-old woman. Cytology showed cohesive sheets and three-dimensional cribriform clusters of bland-looking and mitotically inactive ductal cells in a blood-stained background. Scattered multinucleated, osteoclastlike giant cells, some containing hemosiderin granules, were also seen. Myoepithelial cells and naked nuclei were not obvious. The cellular composition was more discernible in liquid-based cytologic preparations. Histologic examination of the excisional biopsy showed an invasive cribriform carcinoma associated with many osteoclastlike giant cells in a hypervascular stroma. CONCLUSION: In view of the extremely low grade cytology of the malignant ductal cells, invasive cribriform carcinoma may closely mimic benign proliferative breast diseases on fine needle aspiration biopsy. Recognition of this special relationship with osteoclastlike giant cells, which are rarely present in certain subtypes of breast cancer but not benign lesions, can help to arrive at a correct cytologic diagnosis.     

Distribution and role of CD34-positive stromal cells and myofibroblasts in human normal testicular stroma

CD34-positive stromal cells are distributed in various organs including breast, Fallopian tubes, thyroid gland, colon, pancreas, and uterine cervix. To elucidate the distribution of CD34-positive stromal cells, smooth muscle cells, and myofibroblasts in normal human testis, we examined 48 testes obtained by autopsy and operation, including five fetal, one neonatal, and 42 adult cases without evident testicular lesions, using a streptavidin-biotin immunoperoxidase technique. The expression of alpha-smooth muscle actin (ASMA), h-caldesmon, CD34, and CD31 were immunohistochemically examined in all cases. The tunica albuginea and the inner layer of seminiferous tubules in adult testis were predominantly composed of myofibroblasts. Smooth muscle cells were also scattered throughout these sites in some cases. CD34-positive stromal cells were abundant, and they formed a reticular network around the seminiferous tubules and Leydig cells as well as the outer layer of seminiferous tubules. Moreover, myofibroblasts and the CD34 reticular network were already present in the testicular stroma during fetal or neonatal development. Double immunostaining of fetal, neonatal and adult testes using ASMA and CD34 confirmed that myofibroblasts and CD34-positive stromal cells were present in the inner and outer layers of peritubular tissue, respectively. This distribution and cytological identification was also confirmed by an ultrastructural study of four cases. Finally, CD34-positive stromal cells and myofibroblasts are major components of human testicular stroma.     

The distribution of myofibroblasts and CD34-positive stromal cells in normal renal pelvis and ureter and their cancers

In this article, we examined the distribution of myofibroblasts and CD34-positive stromal cells in normal renal pelvis and ureter and their cancers using immunohistochemistry. Eighteen tumors and normal tissues apart from the main tumor were examined. In the wall of normal renal pelvis and ureter, no myofibroblasts were observed through all layers, but CD34-positive stromal cells were observed in the deep area of lamina propria, muscular layer and adventitia. In the stroma of renal pelvic and ureteral cancers, myofibroblasts were distributed in fifteen tumors and were absent in three tumors. All three tumors containing no myofibroblasts in the stroma were non-invasive type and all invasive cancers contained myofibroblasts in the stroma. CD34-positive stromal cells were consistently absent in the stroma of cancers, irrespective of the invasiveness. Finally, myofibroblasts are major stromal components in renal pelvic and ureteral cancers, particularly in invasive cancers, and CD34-positive stromal cells are consistently absent or lost in the stroma of their cancers. These findings suggest that the invasion of renal pelvic and ureteral cancers may cause the phenotypic change of stromal cells.     

CD44及CD24在乳腺癌组织中的表达及与临床病理特征的关系研究

目的:探讨肿瘤标志因子CD44及CD24在乳腺癌组织中的表达及与临床病理特征的关系。方法:选择从2015年1月到2017年1月在我院接受手术治疗的乳腺癌患者80例纳入本次研究,另选同期在我院治疗的导管原位癌患者30例,小叶增生患者20例及导管单纯增生患者20例的组织提取标本进行对照,分析CD44及CD24在乳腺癌组织和不同病变类型中的表达,并分析CD44~+/CD24~-细胞在癌症免疫分型中的表达以及CD44~+/CD24~-细胞与乳腺浸润导管癌相关病理特征的关系。结果:乳腺癌组织内的CD44阳性率为52.50%,CD24的阳性率为57.50%,均显著高于癌旁组织的11.25%和15.00%,差异均有统计学意义(均P0.05)。CD44及CD24在导管原位癌及乳腺浸润导管癌中的阳性率高于小叶增生和导管单纯增生,导管原位癌的阳性率高于乳腺浸润导管癌,差异均有统计学意义(均P0.05),且CD44在乳腺浸润导管癌不同分化类型中的阳性率差异有统计学意义(P0.05)。CD24在乳腺浸润导管癌不同分化类型中的阳性率差异不显著(P0.05)。CD44~+/CD24~-细胞在不同癌症免疫分型以及不同分化中的阳性率比较差异均有统计学意义(P0.05)。CD44~+/CD24~-细胞与乳腺浸润导管癌患者的年龄、月经状态、肿瘤直径、淋巴结转移以及远处转移之间均无明显关系(均P0.05)。结论:CD44及CD24在乳腺癌组织内存在较高的阳性率,且CD44~+/CD24~-在乳腺原位癌及低分化的乳腺癌组织内具有更高的阳性率,临床上可尝试通过监测CD44~+/CD24~-的阳性表达情况评价患者的病情及预后。     

Simultaneous bilateral breast carcinoma: Histopathological characteristics and CD44/catenin-cadherin profile

AIMS: Family history of breast carcinoma, multicentric tumor foci in one breast, and in situ lobular carcinoma increase the risk of bilateral breast cancer (BBC), synchronous or metachronous. Synchronous tumors are designated as simultaneous breast carcinoma if they appear at the same time. The CD44 family and cadherin/catenin immunophenotype of this group of BBCs has not yet been evaluated. The aim of this study was to compare clinicopathological characteristics and immunohistochemical profiles of simultaneous BBC and corresponding lymph node metastases in eight patients. METHODS AND RESULTS: In toto 15 primary and 9 metastatic tumors were evaluated. The expression of CD44 variant isoforms, beta-catenin, E, P and N-cadherin were evaluated by immunohistochemistry. Rare types of breast carcinoma were frequent in this group of patients. There were 6 pleomorphic lobular, 5 invasive ductal of usual type, 3 atypical medullary carcinomas, 2 mucinous and one invasive micropapillary carcinoma. The expression CD44v6 was most frequent, followed by CD44v3-10, CD44v5, and CD44v3. CD44v4 was generally not expressed. E-cadherin was expressed in 80% primary tumors, 40% expressed N-cadherin, and 66% expressed P-cadherin. CONCLUSIONS: Generally, simultaneous carcinomas had different morphology and different immunophenotype. Each primary tumor was more similar to its corresponding metastatic tumor than to the contralateral primary tumor.     

乳腺浸润性微乳头状癌的研究现状

乳腺浸润性微乳头状癌(IMPC)是乳腺浸润性癌的一种特殊类型,其发生率低,临床表现及影像学特征与普通的乳腺浸润性导管癌没有显著区别。这种病理类型可与普通浸润性导管癌混合出现,也可表现为单纯的浸润性微乳头状癌。但浸润性微乳头状癌具有独特的组织学形态及分子结构,决定了其病理学分级较高、易于发生淋巴结转移的侵袭性生物学行为特点。多数浸润性微乳头状癌在影像学上表现为边缘不清的不规则肿块影,常伴有微小钙化。其特征性病理形态为细胞膜上皮抗原(EMA)在肿瘤细胞簇外周的细胞和基质中腔隙边缘特异性染色,同时显微镜下瘤细胞表面发现微绒毛结构,说明了瘤细胞簇周围的空隙样结构实际上是管状腔隙,瘤细胞呈"极向倒转"方式排列。IMPC具有高度淋巴血管浸润倾向,局部复发率高,是一种预后较差的类型。本文对近年来关于乳腺浸润性微乳头状癌的研究进展进行了综述。     

Malignancy-associated changes in breast tissue detected by image cytometry.

In several tissues, nuclear differences have been described in normal-appearing cells from patients with invasive carcinomas compared to cases without invasive carcinoma, a phenomenon known as malignancy-associated changes (MACs). The aim of this study was to determine the presence of malignancy-associated changes in breast tissue. Image cytometry was performed on Feulgen stained tissue sections of patients with usual ductal hyperplasia with (n = 30) or without (n = 41) adjacent invasive breast carcinoma. Nuclear features of normal-appearing cells as well as of usual ductal hyperplastic cells were separately compared between the two groups. Many features of normal-appearing epithelial cells were significantly different between cases with and without invasive cancer. Significant differences were also found by measuring ductal hyperplastic nuclei instead of normal-appearing nuclei. Cases with or without cancer could be distinguished with a classification accuracy of 80% by discriminant analysis using 2 nuclear features derived from ductal hyperplastic cells. In conclusion, image cytometry on breast tissue sections shows that malignancy-associated changes can be found in normal as well as in usual ductal hyperplastic breast cells. This could be clinically relevant for the detection of occult breast cancer, for the prediction of risk in these lesions, and to monitor the effect of chemopreventive agents.     

The appearance of myofibroblasts and the disappearance of CD34-positive stromal cells in the area adjacent to xanthogranulomatous foci of chronic cholecystitis

We investigated the distribution of myofibroblasts and CD34-positive stromal cells in normal gallbladder and its pathological conditions (cholecystitis, n=25) using immunohistochemistry and in situ hybridization. In the wall of normal gallbladder, myofibroblasts were generally absent from all layers, but many CD34-positive stromal cells were observed in the connective tissue layer. In chronic cholecystitis with mild perimuscular fibrosis, a small to moderate number of myofibroblasts appeared in the mucosal layer. In chronic cholecystitis with marked perimuscular fibrosis, a small to large number of myofibroblasts appeared predominantly in the connective tissue layer, whereas the number of CD34-positive stromal cells decreased at the same location, although the number of myofibroblasts increased. In chronic cholecystitis with xanthogranulomatous foci, a small to large number of myofibroblasts were observed in the periphery of the xanthogranulomatous reaction and adjacent area. In contrast, CD34-positive stromal cells were completely absent or were limited to the area just around the xanthogranulomatous reaction. Induction of collagen type I and III mRNA was predominantly observed in the cytoplasm of myofibroblasts associated with the marked fibrosis, which consisted primarily of mature collagen fibers, and in the cytoplasm of myofibroblasts around the xanthogranulomatous reaction, respectively. Finally, myofibroblasts were observed in all subtypes. The increased number of myofibroblasts was most prominent in the connective tissue layer of chronic cholecystitis with marked perimuscular fibrosis or in the area adjacent to xanthogranulomatous foci of chronic cholecystitis. Under these conditions, CD34-positive stromal cells tended to disappear from the connective tissue layer, which exhibited an increase in myofibroblasts.     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast. A case report

BACKGROUND: Invasive micropapillary carcinoma of the breast is uncommon and was characterized only recently. Awareness of this entity and its cytologic appearance is important to allow early diagnosis by fine needle aspiration cytology (FNAC). To our knowledge, only two cases of FNAC of this lesion have been reported in the English-language literature. CASE: An 80-year-old female presented with a firm, nontender mass in the upper outer quadrant of the left breast. FNAC showed ductal carcinoma, and mastectomy showed invasive micropapillary carcinoma. The patient had axillary metastases and received tamoxifen. CONCLUSION: The cytologic features of invasive micropapillary carcinoma are distinctive, with clusters of cells showing hyperchromatic, irregular and crowded nuclei and peripherally located cytoplasm with a rare central lumen. Fibrovascular cores are absent. Although FNAC experience with this lesion is limited, the characteristic cytologic features, including "inside-out" cell clusters, should raise the suspicion of this variant of ductal carcinoma. Differentiation from other papillary lesions and malignancies may be possible, but more experience is needed as the number of reported cases remains limited.     

Fine needle aspiration cytology of lobular breast carcinoma. Comparison with other breast lesions

OBJECTIVE: To analyze the detailed cytomorphology of lobular breast carcinoma and to compare the cytologic smears of benign, borderline and infiltrating duct carcinoma. STUDY DESIGN: Fine needle aspiration cytology (FNAC) smears of histopathologically proven infiltrating lobular carcinoma (ILC), infiltrating ductal carcinoma (IDC), borderline lesions and benign breast lesions were selected for study. Detailed cytomorphologic analysis of the smears was carried out on hematoxylin and eosin- and May-Grünwald-Giemsa--stained slides, and a comparison of results was done. The various cytologic features were also graded semi-quantitatively with the numerical score; logistic regression analysis was done. RESULTS: There were 25 cases of ILC, 30 of IDC, and 10 borderline and 18 benign lesions. Cytologic diagnosis of malignancy on FNAC smears of ILC was offered in 19 cases; of them, 2 cases were diagnosed as ILC. The remaining six cases were diagnosed as borderline (four) and benign lesions (two). Overall sensitivity in detection of malignancy in ILC cases was 76%. FNAC smears of ILC showed moderate (52%) to abundant (32%) cellularity. The cells of ILC were arranged both in clusters and in dissociation (72%). Individual cells were monomorphic (40%) to mildly pleomorphic (60%), and the cells were smaller. The cells showed a smooth, regular nuclear margin; bland chromatin; and indistinct nucleoli. Indian file arrangement was frequently observed (28%). Nuclear molding (28%) and intranuclear inclusions (16%) were also noted. Intracytoplasmic lumina were seen in occasional cases. Logistic regression analysis was carried out, and a comparison between lobular carcinoma and ductal carcinoma, and borderline and benign lesions was done. Logistic regression analysis of cytomorphologic features showed that cellularity and nuclear margin irregularities were the two most important features to distinguish ILC from IDC. In comparison to borderline lesions, cell dissociation was more common in ILC. The salient cytologic features that helped to distinguish ILC from benign lesions was cell size, cellularity, cell uniformity and chromatin pattern. CONCLUSION: There are overlapping cytologic features between ILC, IDC and borderline breast lesions on FNAC smears. Logistic regression analysis may be helpful in this regard.     

Cytomorphological spectrum in gynaecomastia: a study of 389 cases

Cytomorphological spectrum in gynaecomastia: a study of 389 cases The objective of this study was to document the spectrum of cytomorphological features in aspirates from gynaecomastia. During a 22-year period (July 1979 to June 2001) fine needle aspirations (FNA) were conducted on 651 males with a breast lesion. Fine needle aspirate slides from 529 benign cases were reviewed along with the histological sections of 54 cases where available. Of the 529 FNA, 140 were excluded (105 unsatisfactory, five cystic fluid aspirated, 30 inflammatory lesions). In 134 of 389 cases reviewed florid gynaecomastia was observed while the remainder showed benign ductal cells (BDC) in varying quantities from less than five to more than 25 groups. Of the 134 cases with florid gynaecomastia, 49 had a fibroadenoma-like picture (FLP), where a large number of BDC fragments with a staghorn configuration, prominent stromal fragments with contoured stroma and bare bipolar nuclei were seen abundantly in all cases. In 85 cases the features resembled fibroadenomatoid hyperplasia (FH), with only an occasional staghorn configuration of BDC seen in 82% of the cases. In 83% of cases stromal fragments of varying proportions were seen but a contoured stroma was seen in only 3.5% of cases. Both stromal and epithelial atypia were seen in 41% and 86% cases, respectively, of FLP, and in 7% and 69% cases of FH. Columnar cells, apocrine cells and foam cells were seen in approximately similar quantities in both the lesions. Vascularized stroma was seen in 22% of the cases with FLP but in only 4.5% of cases those with FH. Cytohistological correlation performed in 54 cases showed marked variation. Fine needle aspirates showed florid changes in 13 of the 41 cases of simple gynaecomastia and two of the eight cases with florid gynaecomastia on tissue sections. In conclusion, a wide spectrum of morphological features are encountered in FNA from benign male breast lesions. It is important to recognize these to avoid a false-positive diagnosis.     

Automated image morphometry of lobular breast carcinoma

OBJECTIVE: To analyze the role of automated image morphometry (AIM) in distinguishing infiltrating lobular carcinoma (ILC) of the breast from benign, borderline and infiltrating ductal carcinoma (IDC). STUDY DESIGN: Only histopathologically proven lobular carcinoma, ductal carcinoma, borderline lesions and benign breast lesions were selected for the study. There were 19 cases of ILC and 30 cases of IDC, 20 cases of benign lesions (fibroadenoma, 18; fibrocystic disease, 1; and fibroadenosis, 1); 10 cases were borderline lesions (mild epithelial hyperplasia, 3; moderate epithelial hyperplasia, 2; florid epithelial hyperplasia 4; intraductal papillary carcinoma, 1). In all cases hematoxylin and eosin-stained slides were used for AIM. At least 100 cells from each case were subjected to analysis randomly with an image cytometer with Leica Quantimet 600 software (Cambridge, England). Nuclear area, diameter, perimeter, convex perimeter, convex area and roundness were measured in each case with random, unbiased selection of cells and 40 x objectives (one pixel = 0.46 microm). AIM data on the cases were analyzed in relation to final cytologic diagnosis. RESULTS: All the nuclear morphometric features of ILC were much lower than those of IDC and borderline lesions, whereas nuclear morphometric data on ILC were only marginally more than those on benign cases. ANOVA showed that mophometric data were significant (P < .05) in all the variables between ILC and IDC. However, there was no significant difference between ILC, and borderline and benign cases. CONCLUSION: Image morphometry may be useful in distinguishing ILC from IDC on cytologic smears. However, morphometric data may not be helpful in distinguishing benign and borderline lesions from ILC.     

Aromatase and in situ estrogen production in DCIS (ductal carcinoma in situ) of human breast

Ductal carcinoma in situ or DCIS belongs to intraductal proliferative lesions, which are a group of cytologically and architecturally diverse ductal proliferations, typically originating from the terminal duct–lobular units. In these intraductal proliferative diseases, estrogens are considered to be involved in the progression of the disease especially from ductal non-neoplastic hyperplasia to DCIS and possibly development of invasive carcinoma from DCIS. Estrogen receptor (ER) alpha is abundantly expressed in atypical ductal hyperplasia and low grade DCIS. Suppression of estrogenic actions using tamoxifen resulted in inhibition of recurrence of DCIS and/or of progression into invasive carcinoma. Intratumoral estrogen concentration in DCIS determined by liquid chromatography/electrospray tandem mass spectrometry is significantly higher than that in non-neoplastic breast tissues with statistically not lower than that in invasive carcinoma. Aromatase mRNA expression in both stromal and parenchymal cells of DCIS determined by quantitative RT-PCR following laser capture microdissection was also much higher than that in non-neoplastic breast, although lower than that in invasive carcinoma. Immunohistochemistry of aromatase also revealed the similar patterns of immunolocalization as in invasive carcinoma. Aromatase is overexpressed in noninvasive breast malignancies including DCIS and results in elevated concentrations of intratumoral estradiol. These findings could provide the scientific rationale as to employing aromatase inhibitors in the management of ER positive DCIS patients.     

The expression of S100A8 in pancreatic cancer-associated monocytes is associated with the Smad4 status of pancreatic cancer cells

The cross-talk between tumour cells and the surrounding supporting host cells (stroma) is a key regulator of cancer growth and progression. By undertaking 2-DE analysis of laser capture microdissected malignant and stromal components of pancreatic tumours and benign ductal elements, we have identified high levels of S100A8 and S100A9 in tumour-associated stroma but not in benign or malignant epithelia. Immunohistochemical analysis (n = 71 patients) revealed strong expression of both proteins in stromal myeloid cells, subsequently identified as CD14(+)/CD68(- )monocytes/macrophages. Co-immunofluorescence revealed that S100A8 was expressed in a subset of S100A9-positive cells. Correlation of the expression of S100A8 and S100A9 to patient parameters revealed that the microenvironments of tumours which lacked expression of the tumour suppressor protein, Smad4, had significantly reduced numbers of S100A8-immunoreactive (p = 0.023) but not S100A9-immunoreactive (p = 0.21) cells. The ratio of S100A8- to S100A9-positive cells within individual tumours was significantly lower in Smad4-negative tumours than in Smad4-positive tumours (p<0.003). Pancreatitic specimens also contained S100A8- and S100A9-expressing cells, although this was not observed in regions displaying extensive fibrosis. In conclusion, our study provides an extensive analysis of S100A8 and S100A9 in pancreatic disease and highlights a potentially important relationship between pancreatic cancer cells and their surrounding microenvironment.     

Actin-rich (myoepithelial) cells in ductal carcinoma-in-situ of the breast

The distribution of the myoepithelial cells in 32 cases of ductal carcinoma-in-situ (DCIS) of the breast (11 not associated, 21 associated with invasive carcinoma) was investigated with a recently developed immunoperoxidase method for actin. Actin-rich myoepithelial cells were detected at the periphery of some ducts, however, their presence was neither constant nor continuous. Large areas of DCIS were devoid of a myoepithelial cell layer and the neoplastic cells were directly in contact with the stroma. No differences related to the histological pattern of DCIS or the presence and absence of invasive carcinoma were noted. The behaviour of the myoepithelial cells in ductal carcinoma appears different from that observed in cases of lobular carcinoma (Bussolati 1980) and of cystic disease, and may thus be of diagnostic interest. The selective destruction of myoepithelial cells in cases of DCIS might result in a focal disruption of the basement membrane, thus faciliatating invasion.     

Loss of caveolin-1 and gain of MCT4 expression in the tumor stroma: Key events in the progression from an in situ to an invasive breast carcinoma

The progression from in situ to invasive breast carcinoma is still an event poorly understood. However, it has been suggested that interactions between the neoplastic cells and the tumor microenvironment may play an important role in this process. Thus, the determination of differential tumor-stromal metabolic interactions could be an important step in invasiveness.

The expression of stromal Caveolin-1 (Cav-1) has already been implicated in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Additionally, stromal Cav-1 expression has been associated with the expression of stromal monocarboxylate transporter 4 (MCT4) in invasive breast cancer. However, the role of stromal MCT4 in invasiveness has never been explored, neither the association between Cav-1 and MCT4 in the transition from breast DCIS to IDC.

Therefore, our aim was to investigate in a series of breast cancer samples including matched in situ and invasive components, if there was a relationship between stromal Cav-1 and MCT4 in the progression from in situ to invasive carcinoma. We found loss of stromal Cav-1 in the progression to IDC in 75% of the cases. In contrast, MCT4 stromal expression was acquired in 87% of the IDCs. Interestingly, a concomitant loss of Cav-1 and gain of MCT4 was observed in the stroma of 75% of the cases, when matched in situ and invasive carcinomas were compared. These results suggest that alterations in Cav-1 and MCT4 may thus mark a critical point in the progression from in situ to invasive breast cancer.