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Y G Man

Publications and source records attributed to Y G Man.

18 recordsLinked to original sources
PubMed2001

Contributions of intercalated duct cells to the normal parenchyma of submandibular glands of adult rats.

The parenchyma of the submandibular gland in the adult male rat is self-renewing, with most newly formed acinar and granular duct cells believed to differentiate from the rapidly proliferating intercalated duct (ID) compartment. Since the ID cells are phenotypically diverse, based on their different expression of perinatal secretory proteins, we systemically injected tritiated thymidine for 24 hours, and followed the pattern of thymidine distribution in cells by autoradiography and immunocytochemistry of defined cellular phenotypes over a 1-month chase period. Proliferating cells were found within all parenchymal cell compartments; they were most numerous in ID, and primarily in those cells lacking immunoreactivity for the perinatal proteins SMG-B1, -C, and -D. The labeling index (LI) of the ID cells reached a peak at 7 days postinjection, and then decreased over the next 3 weeks. Concurrently, the LI increased significantly in those cells at the junctions of ID with both acini and granular ducts, and also within these larger parenchymal elements. We conclude that the ID cells not reactive for perinatal proteins proliferate to expand the ID compartment, and that ID cells at the ends of the ducts differentiate into both acinar and granular duct cells. Our data provide no evidence for the differentiation of ID cells into cells of striated ducts (SD); however, the small number of excretory duct (ED) profiles seen in our preparations showed extremely high LI (>25%), suggesting that more extensive data might reveal a precursor role for the ED in replacement of SD cells. In addition to the stepwise passage of cells from ID to other parenchymal elements at their junctions, the reported occurrence of occasional clusters of B1-positive acini (BAC) among the typical B1-negative acini had suggested an alternate pathway, in which entire segments of newly expanded ID might develop directly into a recapitulated perinatal stage of B1-reactive cell, pursuant to becoming mature acinar cells. Consistent with this suggestion, the BAC had a fourfold greater LI than typical adult acini; moreover, when analyzed by electron microscopic immunocytochemistry, they appeared similar to the novel perinatal Type III cells both ultrastructurally and in their pattern of B1-immunogold labeling. In contrast, the less common acini showing a sublingual gland phenotype had no significant difference in LI from typical acinar cells. Overall, our results emphasize the importance of the nonimmunoreactive ID cells in normal cellular replacement, and the possibility that ID can undergo en bloc differentiation into replacement acini as well as incremental addition of single cells at the boundaries of ID with acini and with granular ducts.

Animals↗
PubMed2001

Multiple use of slab gels in sequencing apparatus for separation of polymerase chain reaction products.

Attempting to assess whether a decrease of the electrophoresis temperature could prevent or reduce the extent of gel well deformations, and whether the utilization of native polyacrylamide gels (without urea) could speed up the separation of polymerase chain reaction (PCR)-amplified products with an automated 377 DNA sequencer, denatured PCR products were subjected to electrophoresis in 6% native gels under 45 degrees C. Results show that a decrease of the electrophoresis temperature from 51 degrees C (recommended by the User's Manual) to 45 degrees C substantially facilitates the preservation of gel wells, and that all PCR products tested migrate significantly faster in native than in denatured (with urea) gels of the same concentration. The combination of a 6% native gel and a lower (45 degrees C) electrophoresis temperature permits multiple uses of a given gel with consistent results, consequently reducing the electrophoresis time and reagent costs.

DNA↗
PubMed2001

An improved method for DNA extraction from paraffin sections.

The acquisition of comparable quality and quantity of DNA extracts is the prerequisite to the success of comparative genetic analyses. Although several DNA extracting protocols on paraffin sections have been introduced, the importance of deparaffinization, the procedure for obtaining an adequate hematoxylin staining, the significance of the ratio of the cell number to the enzyme volume, and a practical means for monitoring the digestion process have not been sufficiently addressed. These, however, are the most important factors accountable for a failure of DNA extraction. To minimize the impact of these factors, we have developed several unique strategies, including: (1) incubating sections at 80 degrees C for 30-60 minutes prior to xylene treatment, (2) checking each section to insure the complete removal of paraffin; (3) treating hematoxylin stained sections or cells with de-staining solutions; (4) using a micrometer inserted into the eyepiece of a microscope to estimate the number of cells collected and adjusting the enzyme volume according to the cell number; and (5) monitoring the digestion process with a magnifier. With these strategies, we have been able to consistently obtain comparable quality and quantity of DNA extracts which yielded uniform PCR products regardless of variations in tissue embedding and processing.

Clone Cells↗
PubMed2000

Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis.

The high frequency of loss of heterozygosity (LOH) in epithelial cells of mammary ductal carcinoma in situ (DCIS) and IDC is a well known phenomenon, whereas the genetic abnormalities in the mammary stroma and its influence on the epithelial component have not been sufficiently studied. Using the PCR, we examined DNA extracts from microdissected stromal and epithelial tissues of 11 breast samples containing DCIS, including five cases associated with IDC. In each case, the mesenchymal tissue consisting of normal-appearing stroma at a distance from DCIS and IDC or stroma close to either DCIS or IDC was manually microdissected. Epithelial cells from morphologically clear-cut normal ducts and lobules, DCIS, and IDC were also microdissected. Twelve polymorphic DNA markers were tested to identify possible genetic alterations in the mesenchymal and epithelial cells on chromosomes 2p, 3p, 11q, 16q, and 17q. Samples from bilateral reduction mammoplasty from 10 women without any clinical, radiological, or pathological abnormalities were also selected as a control (reduction mammoplasty group). Whereas most cases (8/11, 73%) displayed at least one identical LOH in both epithelial and mesenchymal components, LOH at several loci was noted exclusively in stromal cells. The most frequent genetic alterations in the mesenchymal cells were at chromosomes 17q24, 16q23.1-24.2, 3p14.2, and 11q21-23.2, in 87.5, 62, 60, and 45% of informative cases, respectively. The LOH frequency in the stroma close to cancer ranged from 10 to 66.5% for DCIS and from 20 to 75% of informative cases for IDC. Furthermore, 10 of the 12 polymorphic markers revealed LOH in the stroma at a distance, ranging from 11 to 57% of informative cases. None of the control cases (women without any breast disease) revealed LOH either in the epithelial or in the stromal components. Our findings strongly support the concept of stromal-epithelial interaction in the development and progression of mammary neoplasia. Furthermore, this study suggests that genetic alterations in the stromal cells may precede genotypic changes in the epithelial cells. At least in some cases, the mammary stroma in DCIS or IDC apparently represents a neoplastic interactive component rather than a reactive response to the carcinoma. The frequent allelic loss (LOH) in the mammary stroma, identified in our study, may explain some of the fibroblastic abnormalities previously observed in patients with breast carcinoma or a variety of cancer-associated hereditary diseases. We conclude that the mammary stroma may play a key role in inducing neoplastic transformation of epithelial cells, recapitulating its role in normal mammary duct development.

Breast Neoplasms↗
PubMed2000

Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type ("clinging ductal carcinoma in situ"): a simulator of normal mammary epithelium.

BACKGROUND: Mammary ductal intraepithelial neoplasia (DIN)-flat type ("clinging ductal carcinoma in situ [DCIS]") generally is a subtle epithelial alteration characterized by one or a few layer(s) of atypical cells replacing the native epithelium. The "low power" appearance of DIN-flat type can be misinterpreted easily as "normal" because of the frequent absence of multilayered proliferation and often subtle cytologic atypia. Because it presents as an often unrecognized lesion or in association with tubular carcinoma, to the authors' knowledge the clinical and biologic significance of this lesion has not been well established. METHODS: Using polymerase chain reaction, the authors examined DNA extracts from microdissected areas of 22 cases with extensive "clinging DCIS," including 13 cases associated with infiltrating ductal carcinoma as well as 5 cases associated with more conventional types of DCIS. Eight polymorphic DNA markers with a high rate of loss of heterozygosity (LOH) in classic types of DCIS were selected to identify possible genetic alterations on chromosomes 2p, 3p, 11q, 16q, and 17q. Two cases also were used for the assessment of clonality by means of X chromosome inactivation (methylation pattern of the human androgen receptor [HUMARA] gene). RESULTS: LOH was detected in 17 of 22 lesions (77%), and monoclonality was established in the 2 cases analyzed. The most common genetic alterations were at chromosomes 11q21-23.2, 16q23.1-24.2, and 3p14.2 with LOH in 50%, 45%, and 41%, respectively, of informative cases. The DIN-flat type showed the same genetic alterations (LOH) identified in adjacent in situ and infiltrating ductal carcinoma. In contrast to the DIN-flat type, the perfectly normal mammary epithelium was associated very infrequently (1 of 16 cases; 6%) with LOH. CONCLUSIONS: The DIN-flat type represents one of the earliest, morphologically recognizable, neoplastic alterations of the breast. Recognition of the DIN-flat type is important not only for the early detection of intraductal neoplasia but also to prevent misinterpretation and utilization of this lesion as a normal control in studies. This distinctive lesion could be crucial as an explanation for at least part of the > 20% reported incidence rate of breast carcinoma recurrence observed despite ostensibly "negative" margins of breast biopsies.

Adenocarcinoma↗
PubMed2000

Phenotypically different cells with heterogeneous nuclear ribonucleoprotein A2/B1 overexpression show similar genetic alterations.

Immunocytochemical studies have revealed that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/ B1 in exfoliated epithelial cells is a potentially useful marker of early lung cancer. This study analyzed the correlation of hnRNP A2/B1 expression with molecular alterations in phenotypically different epithelial cells of paraffin-embedded pulmonary tissues. Sections from 20 human subjects were analyzed immunohistochemically for expression of hnRNP A2/B1. Normal-appearing, hyperplastic, and malignant epithelial cells with and without hnRNP A2/B1 expression (n = 78) were microdissected and assessed for microsatellite alterations (MA) and loss of heterozygosity (LOH) (n = 14 markers) as well as for clonality. Results showed that (1) hnRNP A2/B1 immunoreactive cells contained a significantly higher frequency of MA and LOH than did comparable cells that lacked detectable hnRNP A2/B1; (2) over 80% of MA and LOH seen in hnRNP A2/B1 immunoreactive normal-appearing and hyperplastic cells persisted in malignant cells; (3) preliminary analysis of methylation status of the androgen receptor gene in non-neoplastic cells was suggestive of hnRNP A2/B1-expressing cells being of clonal origin; and (4) cells with cytoplasmic hnRNP A2/B1 immunoreactivity had a 3-fold higher frequency of MA and LOH than did cells with nuclear hnRNP A2/B1 immunoreactivity. These findings suggest that phenotypically different respiratory epithelial cells with hnRNP A2/B1 overexpression might be clonally derived, and that the subcellular localization of hnRNP A2/B1 might be an important factor associated with tumor progression.

Cell Division↗
PubMed2000

Fibromatosis of the breast: age-correlated morphofunctional features of 33 cases.

OBJECTIVE: To predict if antiestrogenic agents are useful in the treatment of breast fibromatoses, we undertook an immunohistochemical study of sex steroid hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) and protein pS2 in 33 cases. METHODS: The morphologic and immunohistochemical findings were correlated to patient menstrual status, which was categorized as childbearing age (n = 15), perimenopausal (n = 8), and postmenopausal (n = 10). RESULTS: Fibromatoses in women of childbearing age were more cellular, more mitotically active, and displayed a larger proportion of cells with mild atypia than those in perimenopausal and postmenopausal women. The hormonal status of these 3 groups does not explain the morphologic variations observed in these groups, inasmuch as no immunostaining for any of the hormone receptors was detected in the tumors. CONCLUSIONS: The absence of estrogen receptor and pS2 in breast fibromatoses suggests that antiestrogenic agents are unlikely to be beneficial in the management of these tumors. Assessment of the hormone receptor profile is a useful adjunct in the diagnosis of spindle cell lesions of the breast. Although most spindle cell carcinomas as well as fibromatoses of the breast do not express estrogen or progesterone receptors, the absence of androgen receptor reactivity would favor a diagnosis of fibromatosis over that of myofibroblastoma.

Adolescent↗
PubMed1999

Evidence that Leydig cells in Sertoli-Leydig cell tumors have a reactive rather than a neoplastic profile.

BACKGROUND: Leydig cells are a variable and an inconstant feature of Sertoli-Leydig cell tumors (SLCT). Controversy exists regarding their neoplastic versus reactive nature, and their molecular biologic profile is unknown. METHODS: Six SLCT and one pure Leydig cell tumor were studied. Mitotic counts and immunohistochemistry for Ki-67 were performed in all cases. Leydig cells, neoplastic tissues, and normal nonneoplastic tissues were microdissected. DNA extracts of these samples were assessed for loss of heterozygosity (LOH) by polymerase chain reaction amplification with ten polymorphic DNA markers that have shown high rates of LOH in a variety of human tumors. Three SLCT and the Leydig cell tumor were assessed for clonality by examining the DNA methylation pattern at a polymorphic site on the androgen receptor gene. RESULTS: Leydig cells in SLCT had a low mitotic count (0-1/50 high-power fields [HPF]) compared with the neoplastic stroma (median, 40/50 HPF). Ki-67 was positive in < 2% of Leydig cells in all SLCT, compared with a median of 7% in the neoplastic stroma. Clonality analysis confirmed the monoclonality of the neoplastic cells in the Leydig cell tumor. However, the Leydig cells from three SLCT were polyclonal, whereas the monoclonal nature of the neoplastic Sertoli tubules was confirmed in one of these cases and that of mucinous heterologous elements in another case. The Leydig cell tumor showed LOH at four of the eight loci evaluated. Leydig cells from five SLCT were evaluated: one showed LOH at one locus, two showed LOH at two loci, and the remaining two showed no LOH. CONCLUSIONS: The demonstration that Leydig cells from SLCT are polyclonal strongly suggests that they are nonneoplastic in nature. This is supported by a low proliferation fraction and a lower fraction of LOH compared with the truly neoplastic Leydig cells.

Adult↗
PubMed1999

Expression of the proliferation and apoptosis-associated CAS protein in benign and malignant cutaneous melanocytic lesions.

We have examined the expression of the cellular apoptosis susceptibility protein, a nuclear transport factor that plays a role in apoptosis and cell proliferation, in benign and malignant melanocytic lesions. Tissue samples of 55 formalin-fixed, paraffin-embedded melanoma (primary n=32, metastatic n=23) and of 27 control cases (junctional dermal, compound, Spitz, Reed, blue nevi, balloon-cell nevus, lentigo maligna) were analyzed by immunohistochemistry with anti-cellular apoptosis susceptibility antibodies. The percentage of cellular apoptosis susceptibility-positive cells as well as the intensity on a four-point scale was evaluated. In normal skin, expression of cellular apoptosis susceptibility was primarily found in the basal cell layer of the epidermis. Benign melanocytic lesions that stained positive for cellular apoptosis susceptibility (13 of 27) showed a homogeneously distributed staining pattern with a mean of 5+/-12% cellular apoptosis susceptibility positive cells. Five out of 7 lentigo maligna melanoma, 11 out of 12 superficial spreading melanoma and all acrolentiginous (n=7) and nodular (n=6) melanoma showed immunoreactivity of medium (++) to high ( ) intensity. Vertical growth phases of primary cutaneous melanoma stained stronger than horizontally growing cell clusters. All metastases (n= 23) stained strongly positive, the staining pattern being inhomogeneous. Cellular apoptosis susceptibility detection in clinical stages according to UICC showed an increase from 43+/-34% cellular apoptosis susceptibility positive cells in stage I, to 53+/-26% in stage II, 68+/-24% in stage III and 72+/-24% in stage IV, respectively. Because the expression of cellular apoptosis susceptibility correlates predominantly with advanced stages of melanoma, staining with anti-cellular apoptosis susceptibility antibodies may be useful for diagnosis of melanoma and possibly as an immunohistochemical prognostic factor in cutaneous melanocytic lesions.

Apoptosis↗
PubMed1999

Use of keratin 35betaE12 as an adjunct in the diagnosis of mammary intraepithelial neoplasia-ductal type--benign and malignant intraductal proliferations.

A variety of studies have investigated the role of low molecular weight (LMW) and high molecular weight (HMW) cytokeratin (CK) expression in the normal breast and invasive breast carcinomas. A few studies with small numbers of cases have addressed this issue in intraductal proliferations of the breast. This study investigates the expression of these CKs in a large series of ductal intraepithelial neoplasias of the breast. We examined 150 ductal carcinomas in situ (DCIS), 35 cases of intraductal hyperplasia (IDH), and 15 cases of atypical intraductal hyperplasia (AIDH). Immunohistochemistry was performed using monoclonal antibodies against CK-34betaE12 (HMW CK), CK-8, and CK-19 (LMW CK) on formalin-fixed, paraffin-embedded tissue. The intensity (0, +1, +2, +3) and percentage of positive intraductal cells (0-100%) were multiplied to obtain a score from 0 to 300. The immunoprofiles of IDH, AIDH, and DCIS were categorized into four groups showing negative or low (0-60), moderate (61-100), high (101-200), and very high (201-300) scores. All cases of IDH showed an intensely positive reaction (high to very high scores) for CK-34betaE12. In contrast, 90% of the DCIS showed a negative or only focal and weak reaction (negative or low score) for this antigen. The remaining 10% of DCIS showed a positive immunoreaction for CK-34betaE12 with moderate to high scores. All cases of florid IDH and 96% of cases of DCIS expressed CK-8 intensely with high to very high scores. Although CK-19 was strongly expressed in 97% of cases of IDH (high to very high scores), a very high score was also found in 80% of cases of DCIS that were positive for CK-19. Of the 15 AIDHs, 80% had a negative or only focal reaction (negative or low score) for CK-34betaE12 and the remaining 20% had a moderate to high score for this antigen. Although CK-8 was strongly positive in 87% of cases of AIDH (high to very high scores), only 53.5% of AIDHs showed intense positivity for CK-19. The present study clearly shows that the immunoprofile of IDH is different from DCIS as far as HMW CK is concerned. Although florid IDH is characterized by a diffuse and intense immunoreaction for HMW CK, the lack of or only weak positivity for HMW CK (CK-34betaE12) is, in most cases, a hallmark of ductal carcinoma in situ. The immunoprofile of AIDH is very similar to that of DCIS. The expression of CK-8 and CK-19 is not useful in separating the various categories of ductal intraepithelial proliferations of the breast. We recommend the use of CK-34betaE12 as an adjunct in the diagnosis of a variety of problematic intraductal proliferations of the breast.

Biomarkers, Tumor↗
PubMed1998

Endocrine tumors of the cervix: morphologic assessment, expression of human papillomavirus, and evaluation for loss of heterozygosity on 1p,3p, 11q, and 17p.

BACKGROUND: Cervical endocrine tumors are rare lesions, with a varied diagnostic nomenclature. A recent consensus meeting proposed a standardized terminology. This study evaluated: 1) applicability of histopathologic guidelines; 2) evidence of loss of heterozygosity (LOH) at selected sites; and 3) the presence of human papillomavirus (HPV) detected by nonisotopic in situ hybridization (ISH). METHODS: Thirty-eight cases (patient age range, 19-88 years; mean, 48 years) were retrieved. Outcome data were available for 32 patients. Classification was based on architectural and cytologic features. Tissue was available from 15 cases for LOH analysis with D3S1234(3p14), D3S1289(3p21), THRB(3p24), TP53(17p13), D1S468(1p36), and INT-2(11q13). In ten cases, tissue was analyzed by nonisotopic ISH with HPV probes for types 6/11, 16/18, and 31/33. RESULTS: Tumors were divided into four groups: small cell carcinoma (SCC) (n=25); large cell neuroendocrine carcinoma (LCNC) (n=5); SCC with focal LCNC differentiation (n=3), and carcinoid tumor (n=5). Tumors defined as exclusively or predominantly SCC had a particularly poor prognosis, with 20 patients dead of disease (<6 years after diagnosis) and 6 alive with disease (after <3 years of follow-up). LOH at various 3p loci (3p14, 3p21, and 3p24) was observed in eight cases. One patient demonstrated LOH on 17p(TP53). Eight of ten cases assessed by ISH showed nuclear staining using a combined HPV-16/18 probe. CONCLUSIONS: Cervical endocrine tumors are highly aggressive and can be subdivided into definable categories. LOH at 3p loci is a frequent finding, as is nuclear staining with a combined HPV-16/18 probe. LOH at 17p(TP53 locus) appears to be relatively uncommon, suggesting that p53 mutations may not be developmentally significant.

Adult↗
PubMed1998

LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast.

Papillary carcinoma of the breast is a variant of predominantly intraductal carcinoma characterized by a papillary growth pattern with fibrovascular support. Loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci (including loci reported to show frequent genetic alterations in breast cancer) to determine the frequency of genetic mutations in these tumors and their precursors. Thirty-three papillary lesions of the breast (6 papillary carcinomas, 12 carcinomas arising in a papilloma, and 15 intraductal papillomas with florid epithelial hyperplasia) were retrieved from the files of the Armed Forces Institute of Pathology (AFIP). Tumor cells and normal tissue were microdissected in each case and screened for LOH at INT-2 and p53 as well as several loci on chromosome 16p13 in the TSC2/PKD1 gene region (D16S423, D16S663, D16S665). LOH on chromosome 16p13 was present in 10 of 16 (63%) informative cases of either papillary carcinoma or carcinoma arising in a papilloma as well as in 6 of 10 (60%) informative cases of intraductal papilloma with florid epithelial hyperplasia (IDH). One case showed simultaneous LOH in both the florid IDH and carcinoma components of a papilloma. LOH was not observed at either INT-2 or p53 in any of the papillary carcinomas or papillomas with florid IDH. In conclusion, a high frequency of LOH at chromosome 16p13 (the TSC2/PKD1 gene region) is in both papillary carcinomas of the breast as well as in papillomas with florid IDH, including a case with LOH present simultaneously in both components. These findings suggest that chromosome 16p contains a tumor suppressor gene that frequently is mutated early in papillary neoplasia.

Biomarkers, Tumor↗
PubMed1998

Comparison of loss heterozygosity in primary and recurrent ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is often an indolent disease, although some cases are reported to recur many years after a limited surgical resection. It is not known whether these recurrences reflect a resurgence of residual disease or an independent development of a second tumor in susceptible individuals. Therefore, we conducted a longitudinal molecular study of four women with reappearance of DCIS 2 to 15 years after an initial conservative resection. Loss of heterozygosity (LOH) was characterized in both tumors in each case, using several polymerase chain reaction-amplified microsatellite markers on five chromosomal arms commonly affected in breast cancer. In three cases with ipsilateral recurrent disease, all of the allelic losses seen in the initial tumors were also seen in the recurrent lesions, suggesting a common genetic pathway for the development of both lesions and continuous proliferation of residual disease. The presence of at least one additional LOH in all of the three recurrent tumors, however, suggests that the recurrent tumors developed after genetic progression. In contrast, in one case of DCIS that was followed by the development of DCIS in the contralateral breast 7 years later (a case of bilateral DCIS), unrelated LOH patterns were present in the two lesions. These findings suggest that the reappearance of DCIS in the same breast is most commonly the result of a tumor derived from (but not identical to) the original lesion, with acquisition of additional genetic changes, even when the recurrent lesion manifested itself many years (15 years, in one case) after the initial presentation. Furthermore, genetic progression could be detected in tumors recurring in as little as 2 years after the initial resection.

Adult↗
PubMed1997

Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity.

The histogenesis of carcinosarcomas is controversial, specifically with respect to clonality and cell of origin. To answer these questions, tumor cells from both epithelial and spindle-cell components were microdissected from three cases each of mammary carcinosarcoma and its postulated precursor, carcinoma with spindle-cell metaplasia. Clonality was assessed using the principle of X chromosome inactivation. Loss of heterozygosity (LOH) was evaluated at seven chromosomal loci to assess shared and distinctive genetic alterations for the two components in each tumor. All of the six cases demonstrated identical clonality of the carcinomatous and spindle-cell components, identical to a focus of ductal carcinoma in situ present in one case. LOH for NM23 was detected in both components in one carcinosarcoma, whereas LOH for INT-2 was detected in both components in one metaplastic carcinoma. Differential LOH for D11S904 was present in only the mesenchymal components of these two cases. We conclude that the two components of carcinosarcoma and its precursor are clonal and that the sarcomatous and spindle-cell components arise from mutation of the carcinoma. Presence of differential LOH at D11S904 in only the spindle-cell components suggests that this mutation might be critical to the development of this second phenotype.

Breast Neoplasms↗
PubMed1995

Persistence of a perinatal cellular phenotype in submandibular glands of adult rat.

In the perinatal submandibular gland (SMG) of the rat, Type I cells secrete protein C (89 KD) and Type III cells secrete B1-immunoreactive proteins (20-30 KD); both cell types secrete protein D (175 KD). After the disappearance of both perinatal cell types from the maturing acini, only cells of the intercalated ducts (ID) show strong reactivity for the perinatal antigens. In adult ID, light and electron microscopic immunocytochemical analysis showed that most cells had either C or B1 reactivity, a few had either C and D or B1 and D reactivities, and some cells were unreactive for all of the perinatal proteins. Occasional clusters of "adult" acini, however, were strongly positive for B1 and for D, and these clusters were negative for a typical adult acinar marker, the glutamine/glutamic acid-rich proteins (GRP). Also seen in some preparations were a few anomalous acini with the histological appearance of sublingual (SLG) acini. These were negative for the perinatal and adult submandibular gland marker proteins but reactive with an antibody against SLG mucin. We suggest that the B1-positive acini in the adult SMG consist of newly differentiated replacement cells that have arisen from the ID, and that the anomalous mucous acini are, phenotypically, SLG acini that have differentiated within the SMG parenchyma.

Animals↗
PubMed1989

Promoting effect of croton oil on the induction of cervical and vaginal cancers with herpes simplex virus types 1 and 2 in mice.

Hybrid Swiss virgin mice (Kuan-min strain) were challenged intravaginally with uv-inactivated herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) twice a week for 16 times and subsequently with croton oil or control medium twice a week for 27 times. After a period of 180 days the exposure to HSV-2 plus control medium induced premalignant and malignant lesions of the cervix and vagina in 50.0% of the mice. The exposure to HSV-2 plus croton oil induced similar lesions in 78.2% of the mice. The exposure to HSV-1 combined with either control medium or croton oil induced lesions in 37.2 and 58.3% of the mice, respectively. No malignant lesions were found in the control mice. These results reveal that (1) HSV-1 and HSV-2 have a similar oncogenic potential, and (2) croton oil can promote the induction of cervical and vaginal cancers with HSV-1 and HSV-2. Additionally, these results suggest that the virus-induced carcinogenesis of cervix and vagina might be similar to the classical two-stage carcinogenesis model. This animal model seems to be more suitable for studying the prevention and treatment of cervical and vaginal cancers because the period of this experiment is significantly shorter than that of experiments reported by other investigators and the frequency of the malignant lesion is significantly higher than or similar to that of the same lesion reported in other experiments.

Animals↗
PubMedDate not supplied

Mammary "comedo"-DCIS: apoptosis, oncosis, and necrosis: an electron microscopic examination of 8 cases.

The terms apoptosis and necrosis are commonly used to imply two distinct types of cell death. Apoptosis reflects a genetically mediated. ATP-dependent form of cell death. A passive form of cell death (oncosis) also occurs, often in response to some form of injury. Both pathways can lead to necrosis (postmortem autolytic cell changes). The nature of intraluminal necrosis in mammary ductal carcinoma in situ (DCIS) was evaluated using ultrastructural analysis on paraffin-embedded material of 8 cases with "comedo"-DCIS. In each case, intraepithelial proliferation zones and intraluminal zones (peripheral and central luminal zones) were examined. All cases with "comedo"-DCIS revealed abundant apoptosis, characterized by apoptotic cells showing chromatin condensation and margination with sharply circumscribed, uniformly dense crescents, as well as cytoplasmic condensation. Numerous membrane-bound apoptotic bodies with condensed cytoplasm (with or without nuclear fragments) were also observed. The central luminal zones of "comedo"-DCIS, however, revealed necrotic debris characterized by severe degradative changes, largely devoid of recognizable cell structures. In addition, two cases displayed features of oncosis, characterized by nuclear and cytoplasmic swelling, vacuolization of cytoplasm, and mitochondrial swelling with occasional dense bodies. The results indicate that necrosis (postmortem, secondary degradative cell changes) in "comedo"-DCIS is the end result of either apoptosis (programmed cell death) alone or a combination of apoptosis and oncosis (passive or "accidental" cell death).

Apoptosis↗