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Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression.

PURPOSE: The purpose of this study is to address the hypothesis that activatedmitogen-activated protein kinase (MAPK; extracellular signal-regulated kinases 1 and 2) has a role in breast tumorigenesis, breast cancer progression, and the development of tamoxifen resistance. EXPERIMENTAL DESIGN: H-score analysis and a specific antibody for the immunohistochemical detection of activated MAPK in formalin-fixed, paraffin-embedded tissue sections were used to compare expression in: (a) human breast tumors and their matched adjacent normal breast tissue; (b) primary human breast tumors and their matched lymph node metastases; and (c) primary breast tumors from patients who later proved to be sensitive or resistant to tamoxifen treatment. RESULTS: Active MAPK expression was detected in 48% of primary human breast tumors and was significantly increased in tumors compared with adjacent normal breast (Wilcoxon test, P = 0.027). A significant positive association (chi(2), P = 0.02; n = 55) was obtained between active MAPK and the presence of lymph node metastases. Moreover, increased active MAPK (Wilcoxon test, P = 0.0098) was found in concurrent lymph node metastases compared with primary breast tumors. No significant difference in active MAPK was found in primary tumors of patients who later responded to tamoxifen or did not respond to tamoxifen. CONCLUSIONS: These data suggest that active MAPK is a marker of breast cancer metastasis and has a role in the metastatic process. However, active MAPK is unlikely to be a marker of endocrine sensitivity or involved in de novo tamoxifen resistance.

Blotting, Western↗

Evaluation of the contralateral breast in patients with ipsilateral breast carcinoma: the role of mammography.

OBJECTIVE: To assess the value of mammography in the detection of cancer in the contralateral breast in women with ipsilateral breast carcinoma. MATERIALS AND METHODS: From February 1994 through May 2001, a total of 500 patients with unilateral mastectomy from breast carcinoma had mammograms performed for the first time following mastectomy. We retrospectively reviewed the clinical findings and mammograms of these patients. Four hundred and sixty-four patients were asymptomatic and 36 patients presented with palpable breast or axillary masses. Specific mammographic features of a mass, microcalcifications, architectural distortion and asymmetric density were evaluated. Diagnosis was confirmed by fine needle aspiration biopsy or surgical excision in all patients. RESULTS: Four hundred and sixty-four patients had screening mammograms and 36 patients had diagnostic mammograms. All 36 symptomatic patients had abnormal mammograms. Of these, 12 (33.33%) patients were found to have second primary breast carcinoma, 12 (33.33%) had metastases to the contralateral breast or axillary lymph nodes, six (16.66%) had fibroadenomas, two (5.55%) had abscesses, three (8.33%) had fibrocystic change, and one (2.77%) had axillary node reactive hyperplasia. Of the 464 asymptomatic patients, five (1.07%) had second primary breast carcinoma, five (1.07%) had fibrocystic change, and two (0.43%) had fibroadenomas. The mean age at the time of diagnosis of the first primary carcinoma in the symptomatic patients was 41.9 years (range 35-60 years), and was 43.4 years (range 36-56 years) in the screening group. The mean time interval between the two carcinomas was four years (range one to 13 years) in symptomatic group and 3.4 years (range one to four years) in screening group. The tumour stage in the screened group was in situ (n = 2), stage I (n = 3) and in the symptomatic group was stage I (n = 2), stage II (n = 5), stage III (n = 5). CONCLUSION: Patients who have ipsilateral breast carcinoma have a strong risk to develop a second primary carcinoma in the contralateral breast. Close follow-up of the second breast with careful clinical examination and mammography are necessary for the early detection of cancer.

Adenocarcinoma↗

[Bilateral radical mastectomy for carcinoma of the breast of the stages T0 and T1 (N0, M0) and mammoplasty of both breasts, areola and nipples in a single operation (author's transl)].

Bilateral radical mastectomy and concomitant mammoplasty is a new operative procedure for the treatment of carcinoma of the breast in the stages T0 and the small T1, N0, M0. The advantage of the procedure is the increased extent of the operation, the improved cosmetic result and the single stage of the procedure. Consequently the cure rate is improved and the psychic trauma to the patient is decreased. The operation is more radical since the so-called healthy breast is operated first, including axillary lymphadenectomy and subsequent mammoplasty followed by the same procedure on the so-called diseased breast. If the pectoral muscles are involved, a conventional radical mastectomy has to be done. The diagnosis is made by excisional biopsy and frozen section microscopy. The cosmetic result is improved because both breasts are subjected to the same operation, and lateral differences in shape, volume and consistency of the breasts are eliminated. Cylastic prostheses are inserted as new breasts usually sub-pectorally and rarely subcutaneously. The nipples are surgically reconstructed and pigmented by tattooing. The advantage of this single stage procedure is a single general anaesthesia and less psychic trauma since the patient goes to sleep with the knowledge of waking up with two breasts even though endoprothetic breasts. Post-operative radiotherapy can be applied with the prostheses in place. The principle of cure before cosmetics is preserved. Radical operation of the so-called healthy side is justified because of the above mentioned cosmetic advantages and the 25% incidence of primary or metastatic cancer of the so-called healthy side. The post-operative care of women with a bilateral operation is not a problem since no more breast tissue is left behind. Orthopedic complaints which can occur because of macromastia of the remaining breast are also eliminated.

Axilla↗

Management of cancer of the opposite breast following breast preservation.

Breast preservation has been shown to be a good alternative to mastectomy in selected patients with breast cancer. The purpose of this study was to evaluate the characteristics of cancer developing in the opposite breast to determine if breast preservation should be attempted in that breast as well. From 1979 to 1988, 172 women underwent tylectomy, axillary dissection and irradiation for carcinoma of the breast. All had follow-up mammogram. Mean age was 55 years. Mean follow-up time was 50 months. Thirteen patients (7.6%) developed cancer in the opposite breast. Three cancers were carcinoma in situ, nine were stage I, and one was stage IIa. Nine of 13 patients had breast preservation therapy, and four had mastectomies. Ten patients are alive with no evidence of disease, two are alive with disease and one died with disease. Breast preservation for bilateral breast cancer is a safe alternative if patients can be followed closely.

Adult↗

Estrogen receptor alpha positive breast tumors and breast cancer cell lines share similarities in their transcriptome data structures.

Established human breast cancer cell lines are widely used as experimental models in breast cancer research. While these cell lines and their variants share many phenotypic characteristics with human breast tumors, the extent to which they reflect the underlying molecular biology of breast cancer remains controversial. We explored this issue using a probabilistic rather than heuristic approach. Data from gene expression microarrays were used to compare the global structures of the transcriptomes of three estrogen receptor alpha positive (ER+) human breast cancer cell lines (MCF-7, T47D, ZR-75-1) and 13 human breast tumors (11 ER+; 2 ER-). Linear representations of the respective data structures were obtained by deriving those top principal components (PCs) required to capture > or =80% of the cumulative variance for each data set (M PCs). We then identified those genes most highly correlated with the M PCs (Pearson's correlation coefficient r > or =0.800) and identified a group of 36 genes commonly correlated with both the cell line (M = 5 PCs) and tumor (M = 6 PCs) data structures. All 36 common genes were correlated with PC1 from the breast tumor data: 21/36 genes were correlated with PC1, 14/36 genes correlated with PC2, and 1/36 genes correlated with PC3 from the cell line data. Genes important in defining the data structures include NFkappaB p65, IGFBP-6, ornithine decarboxylase-1, and paxillin. When data from MDA-MB-435 xenografts (ER-) were included in the analysis, we were unable to find any common genes between these xenografts and the breast tumors. These data clearly imply that MCF-7, T47D, and ZR-75-1 cells and ER+ breast tumors share substantial global similarities in the structures of their respective transcriptomes, and that these cell lines are good models in which to identify molecular events that are likely to be important in some ER+ human breast cancers.

Animals↗

Indications for breast-preserving surgery and adjuvant therapy in early breast cancer.

The management of breast cancer has undergone remarkable change over the past two decades. A therapeutic revolution has been fueled by the results obtained from prospective randomized clinical trials. The National Surgical Adjuvant Breast and Bowel Project (NASBP) protocols B-04 and B-06 have clearly demonstrated the efficacy of breast conserving surgery in Stage I and II breast cancer. Through fourteen (NSABP B-04) and 9 years (NSABP B-06) of follow-up respectively, three is no significant difference in either distant-disease free or overall survival between the breast-preserving option and breast removal procedures. These studies not only establish breast-sparing surgery as the preferred local-regional procedure, but more importantly validate the biologic hypothesis governing its use, i.e. breast cancer is a systemic disease and nuances in loco-regional therapy have little impact on survival. Building on this concept, the NSABP instituted clinical trials in the early 1980's designed to evaluate the worth of systemic therapy in node-negative breast cancer. NSABP protocol B-13 examined sequentially administered methotrexate and 5-fluorouracil (MF) versus observation alone in estrogen receptor (ER) negative patients while NSABP protocol B-14 evaluated the worth of tamoxifen versus placebo in ER positive patients. Both of these studies demonstrate a benefit for adjuvant therapy. One can only conclude that adjuvant therapy has altered the natural history of node negative breast cancer. Further clinical trials should expand on advances already achieved and attempt to target therapy to those patients most likely to develop a treatment failure.

Antineoplastic Agents↗

HIV, breast-feeding and under-5 mortality: modelling the impact of policy decisions for or against breast-feeding.

A computer model was developed to assess the impact on under-5 child mortality of breast-feeding practices in developing countries in the context of HIV infection. The model was used to estimate the effect on mortality of cessation of breast-feeding among mothers HIV-positive and mothers HIV-negative at birth, for both urban and rural settings. Using parameter values for a hypothetical East African country, cessation of breast-feeding in urban areas was predicted to result in increases in under-5 mortality of 108% for children of mothers HIV-negative at birth, and 27% for those HIV-positive at birth, with slightly larger increases in rural areas, suggesting that breast-feeding should continue to be promoted. A sensitivity analysis was conducted to identify critical values of key variables for which a review of policies encouraging breast-feeding is indicated. This showed that, even under extreme assumptions, cessation of breast-feeding among mothers HIV-negative at birth (but at risk of acquiring HIV during the lactation period) would increase under-5 mortality. For mothers HIV-positive at birth, the key variables are the additional risk of vertical transmission attributable to breast-feeding, the under-5 mortality rate (U5MR) in breast-fed children, and the relative risk of mortality in non-breast-fed compared to breast-fed children. Depending on the values of these key variables, there may be some urban populations with low U5MR in which the positive and negative effects on under-5 mortality of a policy change are finely balanced. However, no change in policy should be made in these areas until more precise information is available on the key variables, and the many adverse consequences of such a change have been fully explored.

Breast Feeding↗

Breast cancer diagnosis and survival in women with and without breast implants.

The stage at diagnosis and the survival experience of 41 women who developed breast cancer after cosmetic breast augmentation were compared with those of all other patients with breast cancer (n = 13,246) diagnosed in Alberta from 1973 to 1990 (inclusive). The tumors in women with breast implants were smaller (65.9 percent < or = 2 cm) as compared with the tumors in women without implants (34.1 percent < or = 2 cm), but lymph node and distant metastases were equally frequent in the two groups. The distribution of tumor histologic types did not differ significantly between women with or without implants. Women who had an implant were younger at diagnosis of breast cancer compared with women with breast cancer and no breast implants. The relative 5- and 10-year survival rates did not differ significantly between the two groups, and the Kaplan-Meier survival estimate also was similar. It is concluded that women with breast implants in whom breast cancer develops are not diagnosed in a later stage and do not experience an impaired survival as compared with breast cancer patients without implants.

Adult↗

Breast cancer and family history: a multivariate analysis of levels of tumor HER2 protein and family history of cancer in women who have breast cancer.

BACKGROUND: The HER2 gene, located on the long arm of chromosome 17, codes for a protein with the characteristics of a growth factor receptor. In a preliminary study, we reported that high levels of tumor HER2 (erbB-2/neu) protein are associated with a family history of breast cancer (that is, one or more female blood relatives with breast cancer). METHODS: We have now collected a larger number of subjects (94) and performed a multivariate analysis of the independent variables family history of breast cancer, tumor estrogen receptor, age, and tumor DNA index. Family history of breast cancer was assessed by questioning the patient, in many cases by telephone. RESULTS: HER2 levels were significantly higher in women with a family history of breast cancer (p = 0.015, two-tailed t-test). The 27 women with family history were predominantly postmenopausal, mean age 61 +/- 2.3 (mean +/- SEM), versus a mean age of 56 +/- 1.7 for the 67 women with no family history. Of the 27 women with a family history of breast cancer, 13 had a first-degree relative (mother or sister) with the disease. The remaining 14 women had other relatives (grandmothers, aunts, cousins, or a niece) with breast cancer. The results of multiple linear regression analysis, with HER2 as the dependent variable, showed that family history of breast cancer was significantly associated with elevated HER2 levels in the tumors (p = 0.0038), after controlling for the effects of age, tumor estrogen receptor, and DNA index. CONCLUSIONS: The association of family history of breast cancer and elevated tumor HER2 protein suggests that postmenopausal familial breast cancer may be associated with altered HER2 expression.

Biomarkers, Tumor↗

The role of the breast physician in the multidisciplinary breast centre.

The term breast physician was coined in Australia in 1990 to describe a female medical practitioner who is skilled in interpreting screening mammograms and the diagnostic work-up of women with symptomatic breast problems. The Australian Society of Breast Physicians was formed in 1990, and in 1995 became the Australasian Society to incorporate the New Zealand breast physicians. There is now a network of breast physicians throughout Australia who are involved in breast screening clinics or breast diagnostic centres. Thirty women doctors in the United Kingdom work in a similar role. The role of the breast physician is a new, exciting and challenging career option for women doctors. The authors believe that breast physicians have an important role in the diagnosis, treatment and follow up of women with symptomatic breast problems.

Ambulatory Care Facilities↗

Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland).

Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n = 34) and with breast cancer (n = 32). In postmenopausal women, lower dietary intake (P = 0.006) and a smaller concentration of vitamin E in breast adipose tissue (P = 0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r = 0.25, P = 0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.

Adipose Tissue↗

[Breast implants in France. New regulations, and qualitative and quantitative study of breast implants sold between 1995 and 2004].

UNLABELLED: Breast implant surgery is now regulated by health laws, which stopped concerns and debates about the safety of the implants in the 90'. After a 6 years ban, silicone gel-filled implants have been allowed by the Afssaps (a national health agency) in 2001, for use in France. The comeback of the silicone gel implants has been a breakthrough in the breast implant market. GOALS OF THE STUDY: Our goal was to assess breast implant use in France, from 1995 til 2004, a time of deep turmoil for breast implant surgery due to new regulations. METHODS: All manufacturers have been requested to participate in the study and send their confidential data regarding the number and type of implants sold yearly, from 1995 to 2004. RESULTS: Breast implant sales rose by 53% in 2001, and increase by +383% from 1995 to 2004. The total number of breast implants sold in 2004 reached about 61 800. Following the lift on their ban, silicon gel-filled implants became immediately first-choice implants (they represented 72% in 2001 and more than 97% of all implants sold in 2004); saline filled implants are now rarely used. Textured envelopes are more often used (they represented 73 to 97% between 1995 and 2004), and smooth envelopes represented about 15%. CONCLUSION: Health agencies in France and Europe would benefit from a better knowledge of the use and follow-up of breast implants. These are plastic surgeon' or scientific society' responsibilities. A national breast implant registry may be a useful tool to gather information, to improve long-term follow-up and to provide better care to women concerned themselves with breast implant surgery.

Breast↗

Acute and late morbidity of using a breast positioning ring in women with large/pendulous breasts.

PURPOSE: To assess acute and late effects of radiation therapy in women with breast cancer treated with a breast positioning ring. MATERIALS AND METHODS: Fifty-six patients with large and/or pendulous breasts were irradiated using a breast positioning ring. The incidence of acute morbidity was correlated with patient weight and breast 'size'. Cosmesis was scored at > or = 1 year following radiation therapy by the patients. Dose changes in the buildup region under the ring were measured using a computer-controlled scanning system. RESULTS: Moist desquamation (MD) occurred in 60.7% (34/56) of patients treated with the breast ring. The incidence of MD was more common in patients with larger breasts (P = 0.08), the severity necessitating a treatment interruption in 5 out of 56 (9%) patients. Cosmesis at > or = 1 year following radiation therapy was scored as > or = good by all patients. The surface dose under the ring was approximately 85% of the Dmax dose. CONCLUSIONS: The incidence or severity of acute MD in patients treated with a breast positioning ring appears high in patients with large pendulous breasts, and might be related in part, to the increased skin dose due to the positioning ring. To date, there appears to be no significant late normal tissue effects in patients treated with the positioning ring. Additional follow up is needed to assess the long-term consequences of the ring on cosmesis.

Adult↗

Benign breast disease and breast cancer risk: morphology and beyond.

Evidence from clinical follow-up studies has indicated that there is a relationship between the presence of histologically proven benign breast disease and breast cancer risk and that the level of risk varies according to the histologic category of benign breast disease. In particular, proliferative lesions without atypia are associated with a 1.5- to 2-fold increase in risk, whereas atypical hyperplasias are associated with a fourfold to fivefold increase in breast cancer risk. A number of clinical factors appear to modify the risk associated with these lesions, including the time since biopsy, menopausal status, and family history of breast cancer. Recent studies have begun to evaluate the potential role of biologic, molecular, and genetic markers in assessing breast cancer risk in patients with benign breast disease. Additional information derived from clinicopathologic follow-up studies, epidemiologic studies, and molecular and genetic studies will provide new insights into benign breast disease and breast cancer risk.

Breast↗

A rare association of synchronous intraductal carcinoma of the breast and invasive carcinoma of ectopic breast tissue of the vulva: case report and literature review.

Only 17 cases of breast carcinoma arising in vulvar ectopic mammary tissue have been reported. We present a unique case of synchronous pure intraductal carcinoma of the breast (DCIS) and invasive carcinoma of ectopic breast tissue of the vulva. A 53-year-old woman presented with a 2-cm nodule in left labium major of the vulva. A surgical biopsy revealed an invasive carcinoma of ectopic mammary tissue. The mammography showed irregular microcalcifications of the right breast. The patient underwent left hemivulvectomy, bilateral inguinal sentinel lymph node biopsy, and radioguided breast resection (radioguided occult lesion localization) of the microcalcifications. The definitive histology revealed negative inguinal sentinel nodes, no further residual tumor in the vulva, and a high-grade (grade 3) DCIS in the breast. The synchronous occurrence of primary breast carcinoma and ectopic breast tissue carcinoma in the vulva is an extremely rare finding, only once previously being reported and leading to unsolved problems of differential diagnosis. The presence of a pure DCIS of the breast makes this case really unique, definitively confirming the independent primary origin of both mammary tumors. The inguinal sentinel node biopsy avoided a bilateral inguinal dissection.

Breast↗

Hypermethylation of the breast cancer-associated gene 1 promoter does not predict cytologic atypia or correlate with surrogate end points of breast cancer risk.

Mutation of the breast cancer-associated gene 1 (BRCA1) plays an important role in familial breast cancer. Although hypermethylation of the BRCA1 promoter has been observed in sporadic breast cancer, its exact role in breast cancer initiation and association with breast cancer risk is unknown. The frequency of BRCA1 promoter hypermethylation was tested in (a) 14 primary breast cancer biopsies and (b) the initial random periareolar fine-needle aspiration (RPFNA) cytologic samples obtained from 61 asymptomatic women who were at increased risk for breast cancer. BRCA1 promoter hypermethylation was assessed from nucleotide -150 to nucleotide +32 relative to the transcription start site. RPFNA specimens were stratified for cytologic atypia using the Masood cytology index. BRCA1 promoter hypermethylation was observed at similar frequency in nonproliferative (normal; Masood <or=10: 18%, 2 of 11), hyperplastic (Masood 11-13: 15%, 6 of 41), and atypical cytology (Masood 14-17: 22%, 4 of 18; P = 0.79). BRCA1 promoter hypermethylation was not associated with (a) family history of breast or ovarian cancer or (b) calculated Gail or BRCAPRO risk score. BRCA1 promoter hypermethylation was associated with (a) age (P = 0.028) and (b) the combined frequency of promoter hypermethylation of the retinoic acid receptor-beta2 (RARB) gene, estrogen receptor-alpha (ESR1) gene, and p16 (INK4A) gene (P = 0.003). These observations show that BRCA1 promoter hypermethylation (a) is not associated with breast cancer risk as measured by mathematical risk models and (b) does not predict mammary atypia in RPFNA cytologic samples obtained from high-risk women.

Adult↗

Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials.

PURPOSE: Risk factors for local and distant recurrence after breast-conserving therapy and mastectomy were compared to define guidelines for the decision making between both treatments. PATIENTS AND METHODS: The data of two randomized clinical trials for stage I and II breast cancer patients were pooled. The total number of patients in the study was 1,772, of whom 879 underwent breast conservation, and 893, modified radical mastectomy. Representative slides of the primary tumor were available for histopathologic review in 1,610 cases (91%). RESULTS: There were 79 patients with local recurrence after breast-conservation and 80 after mastectomy, the 10-year rates being 10% (95% confidence interval [CI], 8% to 13%) and 9% (95% CI, 7% to 12%), respectively. Age no more than 35 years (compared with age >60: hazard ratio [HR], 9.24; 95% CI, 3.74 to 22.81) and an extensive intraductal component (HR, 2.52; 95% CI, 1.26 to 5.00) were significantly associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion was predictive of the risk of local recurrence, irrespective of the type of primary treatment (P <.01). Tumor size, nodal status, high histologic grade, and vascular invasion were all highly significant predictors of distant disease after breast-conserving therapy and mastectomy (P <.01). Age no more than 35 years and microscopic involvement of the excision margin were additional independent predictors of distant disease after breast-conserving therapy (P <.01). CONCLUSION: Age no more than 35 years and the presence of an extensive intraductal component are associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion causes a higher risk of local recurrence after mastectomy as well as after breast-conserving therapy and should therefore not be used for deciding between the two treatments.

Adult↗

Fibroblast growth factor 7, secreted by breast fibroblasts, is an interleukin-1beta-induced paracrine growth factor for human breast cells.

Keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF7) is known to be a potent growth factor for mammary cells but its origin, cellular targets and mode of action in the breast are unclear. In this study, we carried out studies to determine the localisation of FGF7 and its receptor, and the related growth factor FGF10. We also determined the factors that regulate FGF7 release from stromal cells and the effects of FGF7 on normal and neoplastic breast cells. Using an FGF7-specific antibody which does not react with the FGF7 heparan sulphate proteoglycan (HSPG)-binding site, we showed epithelial and myoepithelial immunohistochemical staining in normal breast sections, and epithelial staining in breast carcinomas. Stromal staining was also detected in some lobular carcinomas as well as a subset of invasive ductal carcinomas. FGF10 and FGF receptor (FGFR)2 immunostaining showed a similar epithelial expression pattern, whereas no stromal staining was observed. We purified normal breast stromal, epithelial and myoepithelial cells and showed that FGF7 stimulated proliferation of both epithelial cell types, but not stromal fibroblasts. We also examined the effects of FGF7 on Matrigel-embedded organoids, containing both epithelial and myoepithelial cells, and showed FGF7 induced an increase in cellular proliferation. Furthermore, conditioned medium derived from stromal cells was shown to increase the proliferation of normal and neoplastic breast epithelial cells, which could be abolished by a neutralising antibody to FGF7. Finally, we showed that interleukin-1beta, but not oestradiol or other oestrogen receptor ligands, caused a dose-related FGF7 release. Further results also indicate that the epithelial localisation of FGF7 and FGF10 in breast tissue sections is likely to be due to their binding to their cognate receptor. In summary, our findings suggest that FGF7 is a paracrine growth factor in the breast. FGF7 is produced by the breast stromal fibroblasts and has profound proliferative and morphogenic roles on both epithelial and myoepithelial cells.

Blotting, Western↗