Proportions Of Stroma Research Articles

Survival impact of pathologic features after salvage lung resection following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer.

Salvage surgery for primary lung cancer is expected to become increasingly common. This study aimed to clarify the survival impact of pathologic characteristics after salvage surgery. Consecutive patients who underwent salvage surgery following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer from 2010 to 2020 were enrolled in this study. The tumor slides were reviewed to determine the size of the tumor bed and the proportions of viable tumor, necrosis, and stroma. A total of 23 patients were evaluated, and 18 had clinical stage IIIB-IV disease. Six received chemoradiotherapy and 17 received systemic therapy alone. A major pathologic response (MPR, ≤ 10% of viable tumor) was observed in 6 patients, and 4 patients achieved a pathological complete response. The 3-year overall and recurrence-free survival rates (OS and RFS) were 78.6% and 59.2%, respectively. There was no significant difference in OS between patients with and without MPR, and even non-MPR patients achieved a favorable 3-year OS of 70.2%. Meanwhile, patients with high (≥ 30%) stroma showed significantly better OS than those with low (< 30%) stroma (3-year OS: 100% vs. 23.3%, p < 0.001). This study showed that the proportion of stroma can be useful for predicting long-term survival after salvage surgery. Further large-scale studies are warranted to confirm the current findings.

Immune Regulation of Mammary Fibroblasts and the Impact of Mammographic Density.

Mammographic density is associated with a 4–6-fold increase in breast cancer risk independent of age and BMI. High mammographic density is characterized by breast tissue with high proportions of stroma comprised of fibroblasts, collagen, and immune cells. This study sought to investigate whether stromal fibroblasts from high mammographic density breast tissue contributes to increased extracellular matrix deposition and pro-tumorigenic signaling. Mammary fibroblasts were isolated from women with high and low mammographic density and exposed to immune factors myeloperoxidase (MPO), eosinophil peroxidase (EPO), transforming growth factor beta 1 (TGFB1) and tumour necrosis factor alpha (TNFA) for 72 h and profiled for expression of cancer-associated fibroblast and extracellular matrix regulation markers. No differences in gene expression profiles or collagen production were observed between fibroblasts with high or low mammographic density, and they did not have a differential response to immune mediators. MPO and EPO significantly increased the production of collagen 1. TGFB and TNFA induced variable changes in gene expression. Fibroblasts cultured in vitro from women with high mammographic density do not appear to be inherently different to those from women with low mammographic density. The function of fibroblasts in mammographic density-associated breast cancer risk is likely to be regulated by immune signals from surrounding cells in the microenvironment.

Biological Mechanisms and Therapeutic Opportunities in Mammographic Density and Breast Cancer Risk.

Simple SummaryPrimary prevention approaches are urgently needed to curb the growing global breast cancer burden. Mammographic density, also known as breast density, is one of the most significant and common independent risk factors for breast cancer. As such, it is an exciting new potential target to reduce the incidence of breast cancer; we could in the future identify women with high mammographic density at an increased risk of breast cancer and take steps to reduce that risk. However, more research is needed to understand the biological mechanisms that underlie high mammographic density and how these might be used to develop new prevention strategies. Here, we review the current knowledge around the biology of mammographic density with a particular focus on immune system factors that could provide new therapeutic targets.Mammographic density is an important risk factor for breast cancer; women with extremely dense breasts have a four to six fold increased risk of breast cancer compared to women with mostly fatty breasts, when matched with age and body mass index. High mammographic density is characterised by high proportions of stroma, containing fibroblasts, collagen and immune cells that suggest a pro-tumour inflammatory microenvironment. However, the biological mechanisms that drive increased mammographic density and the associated increased risk of breast cancer are not yet understood. Inflammatory factors such as monocyte chemotactic protein 1, peroxidase enzymes, transforming growth factor beta, and tumour necrosis factor alpha have been implicated in breast development as well as breast cancer risk, and also influence functions of stromal fibroblasts. Here, the current knowledge and understanding of the underlying biological mechanisms that lead to high mammographic density and the associated increased risk of breast cancer are reviewed, with particular consideration to potential immune factors that may contribute to this process.

Tumour-stroma ratio and 5-year mortality in gastric adenocarcinoma: a systematic review and meta-analysis

Tumour-stroma ratio (TSR) is a novel potential prognostic factor in cancers and based on the proportions of stroma and tumour area. The prognostic value of TSR in gastric cancer is incompletely known. The aim of this study was to estimate prognostic significance of TSR in gastric adenocarcinoma. A search of PubMed (MEDLINE), Web of Science, EMBASE, Cochrane and Scopus databases was performed. A meta-analysis was conducted on five-year survival in gastric cancer patients using inverse variance random-effects methods. The literature search yielded 5329 potential titles, of which a total of seven studies were eligible. Results of six studies including a total of 1779 patients were pooled in the meta-analysis. Only 23 (1.3%) of the patients received neoadjuvant therapy. All six studies had a cut-off of 50% for the proportion of stroma when dividing the patients into low- and high stroma groups. Low TSR (high amount of stroma) was strongly associated with increased five-year mortality (hazard ratio 2.19, 95% CI 1.69–2.85). In conclusion, TSR is a strong prognostic factor in gastric cancer. It could be used to estimate prognosis of gastric cancer patients not receiving neoadjuvant chemotherapy. Further studies including patients receiving neoadjuvant therapy are recommended.

Abstract 2445: Pan-cancer analysis of tumor microenvironment using deep learning-based cancer stroma and immune profiling in H&amp;E images

Abstract Introduction: Tumor purity and deconvolution of cell subsets in tumor environments has been developed based on DNA sequencing data or gene expression profiles. We have developed the artificial intelligence named Lunit SCOPE, identifying and quantifying various histologic components using deep learning from H&amp;E-stained whole slide images. The Lunit SCOPE can define the proportions of cancer epithelium, cancer stroma and immune cells infiltration. We hypothesized that cell proportions analyzed by Lunit SCOPE can accurately predict cell subsets in tumor microenvironment with biologically-reliable results. Method: Deep learning-based H&amp;E image analyzer, Lunit SCOPE, has been trained by 1,191 H&amp;E-stained breast cancer whole slide images with histological components such as cancer epithelium, cancer stroma, normal cells, fat, necrosis, lymphocyte, and fibroblast, annotated by over 10 pathologists. Lunit SCOPE trained by the annotated dataset can profile the cancer stroma ratio and tumor infiltrating lymphocyte (TIL) density in cancer epithelium and cancer stroma. We have selected 21 types of cancers excluding mesenchymal origin cancer in The Cancer Genome Atlas (TCGA). Finally, H&amp;E slides from 7,837 cases have been analyzed by Lunit SCOPE. Result: Pan-cancer analysis has shown that the cancer stroma ratio from Lunit SCOPE was the highest in pancreatic adenocarcinoma. Especially, Consensus Molecular Subtype 4 (CMS4) has shown the highest cancer stroma ratio among colorectal cancer (P &amp;lt; 2.2 x 10-16). The density of tumor infiltrating lymphocyte (TIL) was highest in renal clear cell carcinoma, melanoma and bladder cancer in that order, and lung cancer, esophageal cancer, and head and neck cancer have also presented high TIL density. Moreover, high mutational burden (&amp;gt; 10/Mb) was significantly related to higher TIL density across all cancer types (P = 4.06 x 10-5). In addition, the stromal TIL density was higher in basal type than other subtypes of breast cancer (P = 2.45 x 10-7). Pan-cancer survival analysis showed that higher cancer stroma ratio (HR 1.14, 95% CI 1.04-1.25, P = 0.00419) and higher stromal TIL density (HR 1.17, 95% CI 1.07-1.28, P = 0.000732) were associated with poor prognosis, but higher intratumoral TIL density had good prognosis (HR 0.89, 95% CI 0.82-0.98, P = 0.0126). Conclusion: In this study, TCGA pan-cancer dataset have been analyzed by deep learning-based H&amp;E image analyzer, Lunit SCOPE. As a result, it has been proven that the ratio of cancer stroma is high in pancreatic cancer and CMS4 colorectal cancer, and immunogenic tumors and high mutational burden is related to high TIL density. In summary, Lunit SCOPE has significantly correlated with previously well-defined biological features in pan-cancer analysis. Furthermore, Lunit SCOPE can be developed for the novel tissue-agnostic predictive biomarkers of cancer immunotherapy. Citation Format: Kyunghyun Paeng, Geunyoung Jung, Sarah Lee, Soo Youn Cho, Eun Yoon Cho, Sang Yong Song. Pan-cancer analysis of tumor microenvironment using deep learning-based cancer stroma and immune profiling in H&amp;E images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2445.

Intratumoral stromal morphometry predicts disease recurrence but not response to 5-fluorouracil-results from the QUASAR trial of colorectal cancer.

The biological importance of tumour-associated stroma is becoming increasingly apparent, but its clinical utility remains ill-defined. For stage II/Dukes B colorectal cancer (CRC), clinical biomarkers are urgently required to direct therapeutic options. We report here prognostic/predictive analyses, and molecular associations, of stromal morphometric quantification in the Quick and Simple and Reliable (QUASAR) trial of CRC. Relative proportions of tumour epithelium (PoT) or stroma (PoS) were morphometrically quantified on digitised haematoxylin and eosin (H&E) sections derived from 1800 patients enrolled in QUASAR, which randomised 3239 (91% stage II) CRC patients between adjuvant fluorouracil/folinic acid (FUFA) chemotherapy and observation. The prognostic and predictive values of PoT/PoS measurements were determined by the use of stratified log-rank analyses. A high proportion of tumour stroma (≥50%) was associated with an increased recurrence risk: 31.3% (143/457) recurrence for ≥50% versus 21.9% (294/1343) for <50% [rate ratio (RR) 1.62; 95% confidence interval (CI) 1.30-2.02; P < 0.0001]. Of patients with stromal proportions of ≥65%, 40% (46/115) had recurrent disease within 10 years. The adverse prognostic effect of a high stromal proportion was independent of established prognostic variables, and was maintained in stage II/Dukes B patients (RR 1.62; 95% CI 1.26-2.08; P = 0.0002). KRAS mutation in the presence of a high stromal proportion augmented recurrence risk (RR 2.93; 95% CI 1.87-4.59; P = 0.0005). Stromal morphometry did not predict response to FUFA chemotherapy. Simple digital morphometry applied to a single representative H&E section identifies CRC patients with a >50% higher risk of disease recurrence. This technique can reliably partition patients into subpopulations with different risks of tumour recurrence in a simple and cost-effective manner. Further prospective validation is warranted.

Histological evaluation of the soft palate in dogs affected by brachycephalic obstructive airway syndrome

AIMS: To histologically examine tissue obtained from the thick rostral portion of the soft palate in severely affected brachycephalic dogs, and to quantitatively compare the histological findings with a similar region in control dogs.METHODS: Nine dogs examined for treatment of brachycephalic obstructive airway syndrome (BOAS) were prospectively recruited into the study. Four mesaticephalic dogs were also recruited following euthanasia for reasons unrelated to respiratory or gastrointestinal disease. Palatine tissue was harvested using an elliptical incision extending from the junction with the hard palate to the free caudal edge, and passing axial to the tonsilar crypts. The resected portion was fixed in formalin and stained using H&E. Tissues were examined in transverse section and assessments of the palatinus muscles, interstitium, lamina propria and salivary tissue were recorded. Quantitative analysis of the proportions of palatinus muscle, salivary tissue and stroma was performed using ImageJ image analysis software.RESULTS: When compared to the control dogs, the histological findings of the clinically affected dogs showed a marked increase in acute and chronic muscle degeneration and necrosis. This was typified by swollen, hypereosinophilic fibres with centralised nuclei, myofibre atrophy, loss of cross striations and fragmented sarcoplasm. There was reduced proportions of palatinus muscle (p<0.001) and increased proportions of collagenous stroma (p=0.004) and salivary gland tissue (p=0.046) in the clinical samples, compared to control dogs.CONCLUSIONS: Increased thickness of the palate in dogs with BOAS was not due to muscle hypertrophy but was due to increased stroma within the lamina propria, and increased proportions of salivary tissue. There was also a reduction of muscle mass, especially within the paired palatinus muscles, that may have consequences for palate function.CLINCAL RELEVANCE: The results of this study enable us to start investigating the aetiology of the changes seen in brachycephalic compared to mesaticephalic dogs, which will impact timing and extent of treatment of clinical cases.

High mammographic density is associated with an increase in stromal collagen and immune cells within the mammary epithelium.

IntroductionMammographic density (MD), after adjustment for a women’s age and body mass index, is a strong and independent risk factor for breast cancer (BC). Although the BC risk attributable to increased MD is significant in healthy women, the biological basis of high mammographic density (HMD) causation and how it raises BC risk remain elusive. We assessed the histological and immunohistochemical differences between matched HMD and low mammographic density (LMD) breast tissues from healthy women to define which cell features may mediate the increased MD and MD-associated BC risk.MethodsTissues were obtained between 2008 and 2013 from 41 women undergoing prophylactic mastectomy because of their high BC risk profile. Tissue slices resected from the mastectomy specimens were X-rayed, then HMD and LMD regions were dissected based on radiological appearance. The histological composition, aromatase immunoreactivity, hormone receptor status and proliferation status were assessed, as were collagen amount and orientation, epithelial subsets and immune cell status.ResultsHMD tissue had a significantly greater proportion of stroma, collagen and epithelium, as well as less fat, than LMD tissue did. Second harmonic generation imaging demonstrated more organised stromal collagen in HMD tissues than in LMD tissues. There was significantly more aromatase immunoreactivity in both the stromal and glandular regions of HMD tissues than in those regions of LMD tissues, although no significant differences in levels of oestrogen receptor, progesterone receptor or Ki-67 expression were detected. The number of macrophages within the epithelium or stroma did not change; however, HMD stroma exhibited less CD206+ alternatively activated macrophages. Epithelial cell maturation was not altered in HMD samples, and no evidence of epithelial–mesenchymal transition was seen; however, there was a significant increase in vimentin+/CD45+ immune cells within the epithelial layer in HMD tissues.ConclusionsWe confirmed increased proportions of stroma and epithelium, increased aromatase activity and no changes in hormone receptor or Ki-67 marker status in HMD tissue. The HMD region showed increased collagen deposition and organisation as well as decreased alternatively activated macrophages in the stroma. The HMD epithelium may be a site for local inflammation, as we observed a significant increase in CD45+/vimentin+ immune cells in this area.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0592-1) contains supplementary material, which is available to authorized users.

Backgrounds of origin and character of structural changes in testicles of coalminers of Donbass region

Introduction. For the verification of Chernobyl factor that influences the structure of testicles of Chernobyl accident liquidators that reside in Donbass region it is necessary to establish pre-existing morphological changes due to harmful work conditions in coal mines. The analytical survey of existing literature indicates the lack of actual data on this question.Purpose – to establish mechanisms of changes in morphological and functional states of testicles of coal miners by complex of qualitative and quantitative histological and immunohistochemical studies for further development of differential diagnostic criteria of verification of the Chernobyl impact factor on liquidators of CNPP accident.Material and methods. Testicles withdrawn during forensic medical examination of 57 persons (control group – 30, miners - 27) at ages of 35-45 were taken as the material. Pathohistological research was conducted according to standard methodology. Mice monoclonal antibodies were used to CD34, collаgen type IV, PCNA, chromogranin A and synaptophysine (DAKO). The preparations were studied under Olympus AX70 (Japan) microscope with the use of AnalySIS Pro 3.2 program (SoftImaging Firm, Germany). The morphometric estimation of parenchyma and stroma condition included the determination of 29 parameters in testicles.The results of the research. A comparative morphological study of testicular tissue of the miner group allows us to ascertain the presence of expressed dystrophic and atrophic processes in parenchyma, which correlates with the intensity and partial depletion of function of the interstitial tissue of testes, worsening of microcirculation, expressed development of venous stasis. Against the background of growing average size and proportions of stroma this leads to the increased ratio of vascular and tubular, vascular and epithelial, stromal and parenchymal components. Consequence of malfunctioning in sperm maturation is the increase in the number of spermatogonia, primary and secondary spermatocytes and Sertoli cells, reducing the number and proportions of spermatids.Identified changes must be taken into account when studying the structure of testicular tissue of liquidators, which have in their anamnesis indications of underground labour experience in a mine not less than 5 years. This will allow evaluating the patterns of morphogenesis objectively and developing appropriate differential diagnostic criteria of verification of Chernobyl impact factor. The restrictions of the use of the given method are defined by expressed mosaic of the revealed changes. High values of coefficients testify this. 8 of the 29 analyzed parameters didn’t have statistically significant differences.Conclusions. Advanced study in the field of differential diagnostics and objective verification of morphological changes in the testicular tissue as the result of different pathological effects, including Chernobyl factor, should be considered as the creation of mathematical model of the structure and morphogenesis of such a complex biological system as testicle.

Endometriosis in menopause: a single institution experience

This study aims to present the clinical characteristics of a series of postmenopausal women with endometriosis and to evaluate the preferential location, extension and histopathological features of the lesions. We retrospectively examined the clinical records of 72 postmenopausal women with endometriosis who underwent surgery between January 1998 and December 2010. The median age of patients at the time of surgery was 58.5 years. Eleven patients (15.3%) had previous history of endometriosis and five patients had previously undergone surgery for this reason. Only two patients included in the study were using hormone replacement therapy at the time of surgery. The most frequent location of endometriotic lesions was the ovary and among patients with endometriomas, 35% (20/57) had different grades of metaplasia, hyperplasia, atypia and endometrioid carcinoma arising in endometriosis. The proportions of epithelium, stroma and hemorrhage in endometriotic lesions were higher in patients with concomitant endometrial or ovarian cancer. Endometriosis should be considered in the differential diagnosis of postmenopausal cystic lesions of the ovary. The administration of exogenous estrogen is not a prerequisite for the presence of endometriosis in postmenopausal women, and histological signs of functionally active lesions were also observed in the absence of exogenous hormone intake.

Tissue composition of mammographically dense and non-dense breast tissue

Mammographic density is a strong risk factor for breast cancer but its underlying biology in healthy women is not well-defined. Using a novel collection of core biopsies from mammographically dense versus non-dense regions of the breasts of healthy women, we examined histologic and molecular differences between these two tissue types. Eligible participants were 40 + years, had a screening mammogram and no prior breast cancer or current endocrine therapy. Mammograms were used to identify dense and non-dense regions and ultrasound-guided core biopsies were performed to obtain tissue from these regions. Quantitative assessment of epithelium, stroma, and fat was performed on dense and non-dense cores. Molecular markers including Ki-67, estrogen receptor (ER) and progesterone receptor (PR) were also assessed for participants who had >0% epithelial area in both dense and non-dense tissue. Signed rank test was used to assess within woman differences in epithelium, stroma and fat between dense and non-dense tissue. Differences in molecular markers (Ki-67, ER, and PR) were analyzed using generalized linear models, adjusting for total epithelial area. Fifty-nine women, mean age 51 years (range: 40-82), were eligible for analyses. Dense tissue was comprised of greater mean areas of epithelium and stroma (1.1 and 9.2 mm(2) more, respectively) but less fat (6.0 mm(2) less) than non-dense tissue. There were no statistically significant differences in relative expression of Ki-67 (P = 0.82), ER (P = 0.09), or PR (P = 0.96) between dense and non-dense tissue. Consistent with prior reports, we found that mammographically dense areas of the breast differ histologically from non-dense areas, reflected in greater proportions of epithelium and stroma and lesser proportions of fat in the dense compared to non-dense breast tissue. Studies of both epithelial and stromal components are important in understanding the association between mammographic density and breast cancer risk.

CONTROL OF LOW-RESOLUTION SCANNING OF OVARIAN TUMOR STROMAL COMPARTMENT

The active search for markers of prognostic impact and therapeutic response is of crucial importance in oncology. The amount of stroma is a potential indicator with a significant impact on tumor growth. To solve the problems linked to tumor heterogeneity and, hence, of quantization at the microscopic level, we developed an image-analysis strategy dedicated to estimating the proportion of tumor connective tissue in whole histological sections at low resolution. 2,700-dot-per-inch numerical images were acquired with a calibrated slide scanner and automatically analyzed. We performed a quality control in order to evaluate the efficiency of the proposed method of analysis at the selected resolution. The point-counting method and the interactive drawing of stroma limits on equivalent mosaic microscopic images were "the gold standards." The proportions of stroma estimated on microscopic images (magnification with a 4× objective corresponding to 16,200 dots per inch) and on slide scanner images (2,700 dots per inch) through point counting stereology or manual delineation were equivalent (p &lt; 0.0001). The results obtained through automatic image processing of scanner images were also close to the gold standard (95% correlation, p &lt; 0.0001). The proposed method makes it possible to estimate the stroma amount of ovarian carcinomas in whole histological sections with a simple, fast, and low-cost acquisition device.

Multiple Pulmonary Chondromas in a Young Female Patient: A Component of Carney Triad

Chondromas of the lung are rare benign tumors, and fewer than 100 cases with multiple chondromas have been reported since Bateson1 reported the first case. In 1977, J. Aidan Carney from the Mayo Clinic described pulmonary chondroma associated with gastrointestinal stromal tumors (GISTs) and extraadrenal paraganglioma as a syndrome, which was subsequently called the Carney triad.2 Sporadic case reports and a recent analysis demonstrated that the chondromas in the Carney triad usually occur in young women and are multiple, small, peripheral and not endobronchial, and commonly calcified.2,3 As most of the patients with Carney triad are asymptomatic and the pulmonary neoplasm(s) are usually found as incidental lesions on chest radiography, the diagnosis of Carney triad should be considered when multiple pulmonary chondromas are identified. Here, we report a case of Carney triad that initially presented with multiple lesions of the left lung.

A detailed morphologic and immunohistochemical comparison of pre- and postmenopausal endometriosis

Background:Endometriosis depends on oestrogenic stimulation for its continued growth, accounting for its prevalence during reproductive years. There is doubt among clinicians regarding its existence in postmenopausal women in the absence...

Quantitative Assessment of Gastric Antrum Atrophy Shows Restitution to Normal Histology after Helicobacter pylori Eradication

Background/Aims: Grading gastric mucosal atrophy in antrum biopsy specimens remains a controversial subject because of limitations in interobserver agreement. We previously described a reliable, quantitative method for grading atrophy of the corpus mucosa with excellent reproducibility and good correlation with the Sydney scores. The aims of the present study were to evaluate the applicability of this method for the grading of antral atrophy and to study the effect of Helicobacter pylori eradication on the antral mucosa. Methods: Antrum biopsy specimens were collected from 71 gastroesophageal reflux disease patients at baseline and after 3 and 12 months. After the first endoscopy, all subjects were treated with omeprazole 40 mg daily for 12 months. After randomization, 27 of the 48 H. pylori-positive patients additionally received eradication therapy. In 182 hematoxylin-eosin-stained specimens, which were of sufficient quality, the proportions (volume percentages) of glands (VPGL), stroma (VPS), infiltrate (VPI), and intestinal metaplasia in the glandular zone of the antrum mucosa were measured using a point-counting method. In these specimens, mucosal atrophy was assessed by two experienced gastrointestinal tract pathologists (E.B. and J.L.) according to the updated Sydney classification as either nonatrophic mucosa (n = 47) or as mild (n = 29), moderate (n = 50), or marked (n = 56) atrophy. In addition, a group of 23 cases with difficult-to-classify grades of atrophy were included. Results: The mean VPGL decreased with increasing Sydney grades of atrophy (p < 0.001), while the mean VPS and VPI increased (both p < 0.001). After H. pylori eradication, even the cases with the lowest VPGL regressed to normal levels. Conclusions: Overall, a low VPGL correlates with increasing grades of antrum mucosal atrophy. The present data indicate that gastric mucosal atrophy is reversible, since almost all cases showed regression of VPGL after H. pylori eradication. The cases with difficult-to-classify grades of atrophy showed significantly lower VPGLs and higher VPIs than the reference cases.

Rapid quantitative assessment of gastric corpus atrophy in tissue sections

Background/Aims—Grading of Helicobacter pylori induced atrophic gastritis using the updated Sydney system is severely limited by high interobserver variability. The aim of this study was to set up a quantitative...

Neoangiogenesis and squamous cell carcinoma of the tongue

A tumour can only successfully propagate if it develops its own blood supply. Human cancers show a great propensity for stimulating neoangiogenesis through a variety of mechanisms. The present study investigates the relationship between neoangiogenesis, metastasis and survival in 51 patients with tongue cancer resected surgically, 26 of whom had lymph node metastases treated by radical neck dissection. The vessels were immunolabelled for CD34. Two parameters were studied: the vessel count/mm-2 (VC) and the vessel count corrected for the relative proportions of carcinoma and stroma (VV). The data were analysed by uni variate and multivariate methods. The median VC was 35 and the VV was 103. Patients with neck node metastases tended to have a lower VV (93) than those with no metastases (114) (P = 0.0489). The tumour specific survival of the whole groups of patients was 59% (95% confidence intervals, 37–74%) and not surprisingly the patients with neck node metastases had a poorer survival than those without neck node metastases (,P = 0.0083). Cox’s proportional hazards model demon strated that patients with a low VC index tended to have a good prognosis (P = 0.0234). Previous studies of neoangiogenesis in head and neck squamous carcinoma have been limited and the present investigation suggests that VV is associated with metastases, and that VC may be an indicator of prognosis.

Oestrogen receptor in glands and stroma of normal and neoplastic human endometrium: a combined biochemical, immunohistochemical, and morphometric study.

Cryostat sections of unfixed human endometrial tissue from normal, hyperplastic, and carcinomatous endometrium were assayed for oestrogen receptor content using a radiolabelled oestradiol binding assay with isoelectric focusing to separate receptor proteins. The proportions of myometrium, stroma, and glandular tissue were estimated in adjacent sections by point counting. Further cryostat sections were stained for oestrogen receptor immunohistochemically with a monoclonal antibody and the relative staining intensity of the various tissue components assessed. The area proportions and relative immunohistochemical staining intensity of each tissue component in the cryostat sections were then used to adjust the biochemical results and derive separate values of oestrogen receptor content in myometrium, glands, and stroma. The greatest difference in oestrogen receptor content through the menstrual cycle and between normal, hyperplastic, and malignant endometrium occurred in the glandular element.

On the nature and incidence of goitre in Finnish dairy calf population

In 1968, thyroid glands were obtained from young dairy animals born and raised in the areas of various Agricultural Societies of Finland. Breed, sex and carcass weight were recorded for each case. The thyroids were weighed and preparations made for the histological examination. The relative proportions of epithelium (E %), colloid (C %) and stroma (S %), and the height of the epithelial cells (Eμ), were estimated with histometric methods, and the absolute amount of epithelial tissue in grams per gland (Eg) was calculated. The relative size of the follicles (FN) was also determined. The glands were classified, on the basis of prevailing histological characteristics, into activity groups indicated by numbers from 1 (low) to 6 (high). The glands in groups 5 and 6 were considered histologically as abnormal. The data included both Ayrshires (375 ♂ and 239 ♀) and Finncattle (276 ♂ and 234 ♀), and was characterized by the following mean and range values: carcass weight 66.6 kg (7—214), thyroid weight 12.95 g (2.1—130.0), E % 26.1 (14.4—88.2), C % 70.2 (4.1—85.1), S % 3.7 (0.9—14.6), Eμ 5.0 (2.2—22.5), Eg 3.77 (0.44—98.15), FN 21.9 (9.0—84.7), histological activity 3.0 (1—6). Data obtained from the Ayrshire herd of the Viik Experimental Farm was used as a control material for this study. The correlation study revealed that breed and sex had very little effect on the various thyroid characteristics. Carcass weight, on the other hand, correlated significantly with all other thyroid characteristics except the E %. In order to evaluate the geographic distribution of goitre the data was divided into 15 groups according to the Agricultural Society in whose area the animals were born and raised. Effect of carcass weight on the weight, Eg, and histological activity of the thyroid was first eliminated (e.g. by calculating the deviations from the respective control values) before the 15 groups were comparable with each other. Investigations revealed that the thyroid weight, Eg, and E % were raised and the percentage of histologically abnormal glands was high in the Agricultural Societies of the District of Nyland &amp; Nyland’s Swedish, the District of Tavastland, East-Tavastland, the District of Mikkeli, and North-Karelia. On the other hand, hardly any or no signs of goitre were found in the Agricultural Societies of Satakunta, Tavastland-Satakunta, and Kuopio. Attention was also paid to the consumption of iodized mineral salt mixtures by cattle in the various Agricultural Societies. The extent of variation found in the consumption rate was not, however, large enough to explain satisfactorily the differences in the goitre incidence. Since the mean consumption rate in whole Finland in 1967 was only 1/3 of that of the control herd, it is concluded that the amounts of supplemental iodine in the cattle rations should be considerably increased.