Eccrine ductal and acrosyringeal differentiation of the breast epithelium—a lesion associated with some metaplastic breast carcinomas

Two cases of metaplastic breast carcinoma associated with eccrine ductal metaplasia in the surrounding breast tissue are reported. The metaplastic epithelium deviated from the normal in its immunophenotype not expressing glandular cytokeratins (Cam 5.2) and estrogen receptors, being maspin-positive, and resembling morphologically different segments of dermal eccrine duct and acrosyringium. In addition, in one of the cases, basalioma-like intraductal cell proliferation was observed, also showing focal acrosyringeal differentiation. The invasive carcinomas, one of them representing “syringomatous squamous tumor of the breast” while the other diagnosed as high-grade metaplastic carcinoma, also showed focal eccrine and acrosyringeal differentiation and intensive diffuse maspin expression. These previously unrecognized metaplastic changes of the breast epithelium may represent precursor lesions of certain types of metaplastic breast carcinomas.     

Are centrosomal abnormalities correlated to DNA ploidy in breast cancer?

ADN ploidy was shown to play a role in genomic instability of cancer cells and prognosis. The implication of the centrosome in the cell cycle was also described. Therefore, new prognostic factors could be suggested for a better-tailored therapy. The purpose of this study is to search for correlation between centrosomal abnormality and ADN ploidy in breast cancer. Cell prints were prepared from cell culture of mesothelial ascitis, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Fresh cell prints were also obtained from cases with invasive carcinoma. The centrosome was labelled by an indirect immunofluorescence assay using anti-γ-tubulin antibody and F(ab')(2) FITC before quantification with fluorescence microscopy. ADN ploidy was scored with DNA index obtained by means of flux cytometry. The normal mesothelial cells (94% of cells with only one centrosome) and the diploid cell line MRC5 (68% of cells with two centrosomes) were used as controls. DNA ploidy was found to be correlated with centrosomal abnormality in MCF7 cell line (64% of cells had more than three centrosomes) but not in the 10 cases of invasive ductal carcinoma analysed in this study. The absence of correlation between DNA ploidy and centrosomal abnormality in breast cancer samples may be due to the small numbers of cases, the cell prints or tumorigenesis. Correlation analysis of a larger number of cases and types of breast lesions to numerical and morphological abnormalities of the centrosome are ongoing.     

Are cortisol concentrations in human breast milk associated with infant crying?

The present longitudinal study is the first to investigate the association between human breast milk cortisol and infant crying over the first three months of life. Higher concentrations of breast milk cortisol were expected to be differentially associated with fussing and crying in boys and girls. At 2, 6, and 12 weeks of infant age, mothers (N = 70) collected a morning sample of their milk and kept a 3‐day diary to measure infant fussing and crying. Cortisol was extracted and quantified from milk samples. Results showed that breast milk cortisol concentrations increased from 2 weeks through 12 weeks of infant age. Milk cortisol was unrelated to the total duration, frequency, and bout length of infant fussing and crying for both boys and girls. Directions for future research aiming to extend our knowledge on the biology of milk cortisol in relation to infant behavior and development are discussed.     

What modifies the relation between tumour size and lymph node metastases in T1 breast carcinomas?

AIMS: To evaluate which pathological and clinical parameters modify the relation between tumour size and lymph node metastases in invasive breast carcinomas < 20 mm. METHODS: In a retrospective study, 1075 patients with pT1 invasive breast carcinoma and with known nodal status were analysed. The size of the infiltrating tumour was microscopically evaluated, and the in situ component was not considered. The additional pathological parameters considered were: tumour grade, peritumoral vascular invasion, multicentricity, and angiogenesis. The immunophenotype of the tumour was determined as: the expression of oestrogen (ER) and progesterone (PR) receptors, p53, and c-erbB2. The patients were grouped by age as follows: < 50, 51-70, and > 70 years old. RESULTS: Three hundred and seventy four patients (34.8%) were node positive. Univariate analysis showed that nodal positivity was significantly correlated with large tumour size (> 10 mm), vascular invasion, grade 2-3, multicentricity, and high angiogenesis (> 100 microvessels/x20 high power frame). No significant correlation was found between nodal positivity and ER, PR, p53, or c-erbB2 status. Interestingly, the association with in situ carcinoma was correlated with lower nodal positivity in tumours presenting equally sized infiltrating components. Age was an independent variable and significantly modified the risk of nodal positivity in tumours < 1 cm. In fact, in patients under 51 years of age, the proportion of nodal positivity in pT1a tumours was sevenfold higher than in older patients. In patients from 51 to 70 years old, nodal positivity correlated with tumour size, and multicentricity was an additional risk factor. CONCLUSIONS: These data suggest that, together with tumour size, the presence of in situ carcinoma, and vascular invasion, age is one of the most important predictors of metastatic diffusion in breast carcinomas.     

Lateral biases in head turning and the moro response in the human newborn: Are they both vestibular in origin?

Head turning after release from the midline and the Moro response to a full-body drop in 15 full-term newborns lying supine on a custom-built platform was studied. While the lateral bias for head turning was not as pronounced as for the Moro response, it was still assumed in the ratio of 2 (right):1 (left) as predicted by Previc (1991). Onset latency and time-to-peak acceleration were both significantly shorter in the right arm during the initial phase of the Moro response. For both measures, this right arm bias persisted over four consecutive elicitations in most infants. Vaginally delivered infants and those born by Caesarean section did not differ in terms of head preference and the two measures of arm advantage. Our main finding was that infants with a right-sided head preference had a consistently shorter onset latency for the right arm. We interpret this association as stemming from a common labyrinthine asymmetry that involves different vestibulospinal pathways for the neck and arm muscles. In general, our findings are discussed in the context of Previc's (1991) left-otolithic dominance hypothesis and Grattan, De Vos, Levy, and McClintock's (1992) model of newborn functional asymmetries. © 1998 John Wiley & Sons, Inc. Dev Psychobiol: 339–349, 1998     

A distinct microvascular pattern accompanied by aggressive clinical course in breast carcinomas: A fact or a coincidence?

The aim of this study was to evaluate the potential relationship of microvascular growth patterns with survival in invasive breast carcinomas.     

What drives breast cancer heterogeneity: oncogenic events or cell of origin?

Breast cancer is known to show considerable inter-tumoural heterogeneity. It is widely accepted that combinations of oncogenic events have a major role in determining tumour phenotype. However, accumulating evidence suggests that the identity of the cell that acquires the first oncogenic event, the so-called cell of origin, may define the molecular subtype of the resulting tumour. Recent work published in the Journal of Pathology by Natrajan and colleagues questions the origin of breast cancer heterogeneity. After studying BRCA1 tumours, they suggest that genomic alterations are not sufficient to determine tumour behaviour. These and other recent observations underscore the importance of defining what is causing tumour heterogeneity, so that appropriate therapy can be given.     

Black bile: Are elevated monoamines an etiological factor in some cases of major depression?

It was hypothesized decades ago that reduced levels of brain monoamines such as serotonin or norepinephrine form, at least in part, a pathophysiological basis for major depression. Consistent with this hypothesis, a conventional strategy used, with varying success, to treat major depression involves administering antidepressant drugs that are thought to boost the synaptic concentration of serotonin and/or norepinephrine. While the reduced monoamine hypothesis is well known but highly controversial and widely considered to be incomplete or simply incorrect, the possibility that elevated monoamines are an etiological factor in some cases of major depression (rather than or in addition to hypomania or mania) has received little attention at all. This paper puts forth the novel hypothesis elevated brain levels of three monoamines – serotonin, norepinephrine, dopamine – are each etiological factors in some cases of major depression. In support of this hypothesis, the paper very briefly reviews relevant data on each of these neurotransmitter systems, including: transporter knockout mice, human genetic association studies, and pharmaceutical studies that enhance or diminish transmitter signaling in either rodents or humans. While all of the published data do not support the hypothesis, there are studies that do for each of the three transmitter systems. The etiological basis of the putative effect of monoamines on depression may be mediated both through genetics and exposure to psychological stress. If the elevated monoamine hypothesis is correct for some persons, pharmaceutical treatment of depression may be significantly improved if the particular elevated monoamine(s) could be identified and then altered on a personalized basis, or perhaps for different putative subtypes of depression. One possibility is that atypical depression involves elevated noradrenergic signaling.     

Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?

Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis‐derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype‐specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine γ‐lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Müllerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three‐dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Are selectins involved in metastasis?

The selectins are a family of intercellular adhesion molecules that mediate the attachment of leukocytes to the endothelial lining of blood vessels. Another biological process that may involve selectins is the adhesion of circulating tumour cells to endothelium in cancer metastasis. This review discusses the evidence for the involvement of E-, P- and L-selectin in the metastasis of different tumour types. It is concluded that, with certain reservations and qualifications, selectins can play a role in metastasis. For example, the evidence for the involvement of E-selectin in breast and colon cancer metastasis is very strong. For the other selectins and tumour types the evidence is less convincing and further investigations are required to clarify the situation. Certainly, selectins are not the only mechanism available for tumours to metastasise. In the future, measurement of selectins could be useful prognostically and manipulation of their levels could lead to new cancer therapies.     

Are some chromosomes particularly good at sex? Insights from amniotes

Several recent studies have produced comparative maps of genes on amniote sex chromosomes, revealing homology of gene content and arrangement across lineages as divergent as mammals and lizards. For example, the chicken Z chromosome, which shares homology with the sex chromosomes of all birds, monotremes, and a gecko, is a striking example of stability of genome organization and retention, or independent acquisition, of function in sex determination. In other lineages, such as snakes and therian mammals, well conserved but independently evolved sex chromosome systems have arisen. Among lizards, novel sex chromosomes appear frequently, even in congeneric species. Here, we review recent gene mapping data, examine the evolutionary relationships of amniote sex chromosomes and argue that gene content can predispose some chromosomes to a specialized role in sex determination.     

Are some motives more linked to suicide proneness than others?

This research examines the importance of assessing motivations that crisis patients attribute for considering a suicide attempt. For 251 consecutive patients attending a crisis unit, suicide attempters and ideators indicated agreement with each of 14 reasons for attempting suicide. Principal components analysis of these agreement ratings yielded two factor scales of motives: Extrapunitive/Manipulative Reasons and Internal Perturbations. Scores for internal perturbations correlated significantly with patients' wishes to die, clinicians' ratings of patients' suicidal desire and preparation for suicide, and clinicians' overall evaluation of patients' suicidal risk. Associations between internal perturbations and these suicide measures were nonredundant with hopelessness. It is concluded that evaluating a suicidal person's internal reasons for attempting suicide has unique assessment value. © 1998 John Wiley & Sons, Inc. J Clin Psychol 54: 569–576, 1998.     

What happened in the origin of human consciousness?

At some point in its evolutionary history, our species Homo sapiens ceased to be a nonlinguistic, nonsymbolic organism, living in the world as presented to it by Nature, and instead began to exist in a world that it reconstructs in its own mind. Most scientists since Darwin have been content to explain this extraordinary transformation in human consciousness by the operation of natural selection. However, the human fossil and archaeological records indicate that modern human symbolic consciousness is not the culmination of the long trend that natural selection would predict. Instead, it shows that major change in the human past has been episodic and rare and that, as far as can be determined from the archaeological record, the passage from nonsymbolic to symbolic cognition is a recent event as well as an unprecedented one. So recent, indeed, that it significantly postdates the acquisition of modern human anatomy as expressed in skeletal structure. It, thus, appears most likely that the biological (neural) capacity underwriting the radically new behavioral mode arose as an incidental exaptation in the same process that produced the new skeletal structure of Homo sapiens, but that it lay unexpressed until it was "discovered" by means of a cultural innovation, plausibly the invention of language. As in the case of the modern anatomical structure, it appears that the new capacity was initially expressed in Africa and that its various behavioral potentials were sequentially discovered in a drawn-out process that is continuing today. An "accidental" origin of the human capacity helps understand why so many human behaviors have proven self-destructive and contradictory, a feature of our species that reductionist, selection-based scenarios are hard-put to explain.     

Three molecular classifications surrogate to four immunohistochemical markers in 374 invasive breast carcinomas with long follow-up: Which is better?

In the early 21st century, a new way to classify breast cancer appeared, based on their gene expression profiles. Various classifications have been proposed in an attempt to subrogate these molecular groups to an immunohistochemical expression of estrogen and progesterone receptors, HER2 and Ki67. We compared the three major molecular classifications (MCs) of 374 infiltrating breast carcinomas with the assumption that one is better than the others to discriminate the prognosis of patients that are classified by it. We found that [1] there was a significant statistical association with tumor grade and presence of associated HG-DCIS, but with differences in kappa indices [2]; MC3 showed a significant relationship with pathological tumor stage (p = 0.012, CI95% of 0.012–0.017); [3] only MC3 showed convincingly that the observed differences in OS were not due to chance in the univariate analysis (p = 0.04); [4] only MC3 is an independent prognostic factor of OS. In conclusion, these three classifications are not interchangeable; MC3, the only one that includes Ki67 expression in their defining criteria, is better in predicting prognosis than the others.     

Assessing risk communication in breast cancer: Are continuous measures of patient knowledge better than categorical?

Objective

To compare the performance of categorical and continuous measures of patient knowledge in the context of risk communication about breast cancer, in terms of statistical and clinical significance as well as efficiency.

Methods

Twenty breast cancer patients provided estimates of 10-year mortality risk before and after their oncology visit. The oncologist reviewed risk estimates from Adjuvant!, a well-validated and commonly used prognostic model. Using the Adjuvant! estimates as a gold standard, we calculated how accurate the patient estimates were before and after the visit. We used three novel continuous measures of patient accuracy, the absolute bias, Brier, and Kullback–Leibler scores, and compared them to a categorical measure in terms of sensitivity to intervention effects. We also calculated the sample size required to replicate the primary study using the categorical and continuous measures, as a means of comparing efficiency.

Results

In this sample, the Kullback–Leibler measure was most sensitive to the intervention effects (p = 0.004), followed by Brier and absolute bias (both p = 0.011), and finally the categorical measure (0.125). The sample size required to replicate the primary study was 18 for the Kullback–Leibler measure, 23 for absolute bias and Brier, and 37 for the categorical measure.

Conclusions

The continuous measures led to more efficient sample sizes and to rejection of the null hypothesis of no intervention effect. However, the difference in sensitivity of the continuous measures was not statistically significant, and the performance of the categorical measure depends on the researcher's categorical cutoff for accuracy. Continuous measures of patient accuracy may be more sensitive and efficient, while categorical measures may be more clinically relevant.

Practice implications

Researchers and others interested in assessing the accuracy of patient knowledge should weigh the trade-offs between clinical relevance and statistical significance while designing or evaluating risk communication studies.     

ESR1 amplification in endometrial carcinomas: hope or hyperbole?

The ESR1 gene maps 6q25 and encodes for oestrogen receptor alpha, which has been shown to play a pivotal role in the development of breast and endometrial cancer. It has recently been reported that oestrogen receptor alpha expression may be driven in some cases by ESR1 gene amplification and that this phenomenon may be an early event in breast and endometrial carcinogenesis. Although copy number gains of 6q have been reported by several groups, their prevalence, association with oestrogen receptor alpha expression, and clinical implications have been a matter of controversy. Here we discuss the key issues regarding the methods employed in the identification of ESR1 amplification, and briefly review the current literature and recent controversies on the subject of ESR1 amplification in endometrial and breast cancers.     

Are antihistamines useful in managing asthma?

There continues to be a great deal of interest in the anti-asthmatic role of antihistamines. Antihistamines have recently been shown to have anti-inflammatory properties that are more extensive than simply the blocking of histamine receptors. For example, new evidence suggests that the suppression of cell adhesion molecule expression occurs with these drugs. The anti-inflammatory and anti-asthmatic effects of antihistamines have been evaluated in patients with both allergic asthma and rhinitis, given the established association between allergic inflammation of the upper and lower airways, with evidence to suggest that antihistamines have clinically relevant anti-asthmatic properties. As well as conferring benefits in asthma symptom control and the measurement of lung function, studies assessing the effect of histamine receptor antagonists on bronchial hyperresponsiveness suggest that there is bronchoprotection during both methacholine and mannitol challenges. Recently, there has also been considerable interest in the effect of combining an antihistamine with a leukotriene receptor antagonist. This combination has an anti-asthmatic effect that is greater than that of either drug given alone and may be comparable to inhaled corticosteroid therapy.     

Cognitive adaptation theory and breast cancer recurrence: Are there limits?

Relations of the components of cognitive adaptation theory (self-esteem, optimism, control) to quality of life and benefit finding were examined for 70 women (91% Caucasian) diagnosed with Stage I, II, or III breast cancer over 5 years ago. Half of these women experienced a recurrence within the 5 years; the other half remained disease free. Women were matched on age, race, stage of disease, and intervention condition. Baseline perceptions of personal control over illness, but not general self-esteem or optimism, were associated with women's reports of worse physical functioning, worse mental functioning, and less benefit finding 5 years later for recurrent women but not disease-free women. These findings highlight the notion that there may be boundary conditions on the adaptiveness of perceived control.