Primary Epithelial Tumors Research Articles

Glandular Tumors of the Lacrimal Sac: Their Histopathologic Patterns and Possible Origins

To describe and characterize the primary lacrimal sac epithelial tumors of glandular origin, and to describe their possible source from glands in the lacrimal sac and nasolacrimal duct walls. The authors conducted a clinicopathologic study on 14 patients with epithelial lacrimal sac tumors of possible glandular origin. In addition, they reviewed 35 surgical specimens of the lacrimal sac and nasolacrimal duct region and 13 cadaver specimens of the lacrimal sac region. Six of the tumors were benign: four were oncocytomas and two were pleomorphic adenomas. Eight of the tumors were malignant: three were oncocytic adenocarcinomas, three were adenoid cystic carcinomas, and two were adenocarcinomas. All tumors were from adults, ranging in age from 38 to 87 years. Twenty-eight of the 47 specimens of lacrimal sac and nasolacrimal duct region showed mixed glands of serous and mucous elements. Although rare, benign and malignant glandular lacrimal sac tumors should be considered in the differential diagnosis of lacrimal sac obstruction. Their possible origin is from the normal glands that exist under the lacrimal sac and nasolacrimal duct epithelium.

Adrenal 4-binding protein in common epithelial and metastatic tumors of the ovary

Adrenal 4-binding protein (Ad4BP) is a transcription factor that regulates the expression of steroidogenic enzymes. Ovarian tumors other than sex cord stromal tumors are occasionally associated with functioning stroma or hormonal abnormalities. To determine the steroidogenic potential of these tumors, the authors determined the immunohistochemical distribution of Ad4BP in 75 patients with primary common epithelial tumors (20 cystadenomas, 15 carcinomas of low malignant potential, and 40 carcinomas), and seven patients with metastatic carcinoma of the ovary. Ad4BP immunoreactivity was observed in intratumoral stromal cells in 3 of 15 (20%) carcinomas of low malignant potential, 26 of 40 (65%) carcinomas, and three of seven (43%) metastatic carcinomas. Ad4BP immunoreactivity was not observed in the stroma of cystadenomas. Among the positive cases, Ad4BP-positive stromal cells were particularly distributed adjacent to invasive carcinomatous glands. Among ovarian carcinomas, mucinous carcinoma showed a significantly higher number of Ad4BP-positive intratumoral stromal cells than did other histological types. Results suggest that invasion of primary or metastatic carcinoma into the ovarian stroma, especially in the case of mucinous carcinoma, may render the stromal cells to acquire the potential of metabolizing and synthesizing steroid hormones.

Epithelial Ovarian Tumors in Young Women Under 35 Years

The aim of this study was to investigate the clinical-pathological pattern of primary malignant epithelial ovarian tumors in women under 35 years old. We have retrospectively analyzed data from 545 patients with these tumors, identifying 49 patients under age 35. We found a higher frequency of borderline tumors and early-stage tumors in young women than in those over 35. The influence of age as a factor in survival was evaluated by comparing the outcome in young patients and in women over 35. The 5-year survival rate, according to stage and aggressiveness factors, was significantly better in young patients. These findings support the concept of a preclinical phase of epithelial carcinoma and show that young women may be selected for conservative surgery, allowing a good quality of life.

Expression of cadherins and alpha-catenin in primary epithelial tumors of the liver

BACKGROUND & AIMS: Cadherins and their associated molecules, such as alpha-catenin, have been shown recently to play a pivotal role in epithelial carcinogenesis. METHODS: The expression of E-cadherin, N- cadherin, and alpha-catenin in 10 normal samples, 28 focal nodular hyperplasias, 9 liver cell adenomas, 65 hepatocellular carcinomas, and 9 cholangiocarcinomas was studied by immunohistochemistry and Western blotting. RESULTS: In the normal liver, hepatocytes expressed E- cadherin and a 129-kilodalton cadherin identified by the anti-N- cadherin antibody GC4. The expression level of alpha-catenin was low. Bile duct cells expressed only E-cadherin and showed high levels of alpha-catenin. The expression of cadherins and alpha-catenin was preserved in focal nodular hyperplasia. In liver cell adenomas, cadherins and alpha-catenin were heterogeneously expressed. In hepatocellular carcinomas, cadherin and alpha-catenin expression was frequently reduced or absent. Alterations in cadherin expression correlated with large tumor size, low grade of histological differentiation, and occurrence of capsular and vascular invasion. In cholangiocarcinomas, neoplastic cells inconstantly expressed E-cadherin and alpha-catenin. CONCLUSIONS: Alterations of cadherin and alpha- catenin expression are frequent in liver cell adenomas and primary liver carcinomas. Their incidence in hepatocellular carcinomas is of prognostic significance. (Gastroenterology 1996 Apr;110(4):1137-49)

Immunohistochemical expression of c-Met in primary and recurrent human ovarian epithelial neoplasms.

Immunohistochemical expression of c-Met in primary and recurrent human ovarian epithelial neoplasms.

Adenocarcinoma of Minor Salivary Gland Origin with Skeletal Metastasis in a Child

Primary epithelial neoplasms of the salivary gland in children are uncommon but are well recognized and occur principally in the major salivary glands. The purpose of this report is to document our experience with an adenocarcinoma of the buccal submucosa (one of several sites of minor salivary gland tissue) that metastasized to multiple bones as the initial sites of distant disease after a local recurrence. The clinical history, imaging studies, and microscopic sections including immunoperoxidase studies were evaluated from the primary tumor, local recurrence, and a metastatic lesion from the femur. The histopathologic features and immunohistochemical phenotype of the adenocarcinoma in the buccal submucosa supported its salivary gland origin. This case of adenocarcinoma of the intraoral buccal tissues independent of the parotid gland in a 12-year-old female is an unusual clinical presentation of a salivary gland neoplasm in childhood, and its ability to metastasize to distant skeletal sites is also remarkable in terms of a primary salivary gland carcinoma regardless of age at diagnosis.

Primary Epithelial Tumors of Salivary Glands.Histomorphological and Immunohistochemical Implications.

The predominant amount of research dealing with salivary gland tumors has been the histogenesis of different epithelial tumors and supplementally immunohistochemical and ultrastructural assessments. Salivary gland tumors, both benign and malignant, showed most heterogeneity of histopathology and histochemistry that considered biological roles of epithelial-mesenchymal interactions as biosynthesis of extracellular matrix proteins. Many primary salivary gland tumors histologically consist of most epithelial structures associated with modified or neoplastic myoepithelial cells which have been recognized to be complex properties of epithelial, mesenchymal and other structural components, although normal myoepithelial cells showed more simple properties. Recently, modified or neoplastic myoepithelial cells in salivary gland tumors were not shown to originate from myoepithelial cells and were possible ductal cells in origin. However those uncomprehensive or non-distinct properties of histogenetic concepts in human salivary gland tumors can not be instead of animal studies. Moreover rodent submandibular glands have shown specific structures as granular convoluted tubules which are the source of growth factors or biologically active peptides, and human specimens may have a possibility to synthesize or produce growth factors. Thus the present review deals with critical evidence or possible identification of specific target subjects during histogenesis of salivary gland tumors, as well as different histologic types of tumor lesions without common classification. With the continued interest of salivary gland research under pathologic implication, unique systems for identification or molecular manipulations of salivary gland tumors may provide new opportunities in the health sciences.

The Influence of Combination Chemotherapy on Antigen Expression in Ovarian Cancer

The best treatment results for advanced-stage ovarian cancer patients are obtained with cytoreductive surgery followed by combination chemotherapy. However, the 5-year survival rate of only 20% clearly shows a need for new treatment modalities. At present several modes of immunotherapy for cancer are being explored such as the use of monoclonal antibodies, bispecific antibodies, or specific cytotoxic effector cells, all making use of the presence of tumor-associated antigens remaining, necessary for tumor cell recognition. The antigenic phenotype of human epithelial ovarian cancer after chemotherapy treatment is an important issue in planning potential immunotherapeutic strategies for ovarian cancer. Therefore, we compared the antigen expression in tumor specimens obtained during operation for primary epithelial ovarian tumors and tissue biopsies taken during second-look operations after the administration o[ combination chemotherapy. A total of 60 ovarian tumors, including 44 serous, 3 mucinous, 2 endometrioid, 1 clear cell, 6 mixed, 2 undifferentiated, and 2 granulosa cell tumors, was studied. Frozen sections of the tumor specimens were stained with 15 different monoclonal antibodies by the indirect immunoperoxidase technique and graded semiquantitatively. The results showed only limited differences in antigenic expression in tumor tissue obtained before and after chemotherapy. Because antigen expression was not altered, immunotherapy making use of these antigenic determinants will not be hampered by prior chemotherapy.

Expression of integrin adhesion molecules in normal ovary and epithelial ovarian tumors.

The metastatic potential of a solid tumor is dependent upon its ability to interact with the extracellular matrix. The integrin superfamily is a group of proteins that are fundamental in such interactions and play a major role in cell-cell and cell-matrix adhesion. Localization of the integrin proteins was performed in normal ovary, primary epithelial ovarian tumors and metastatic tumor cells in ascitic samples. Expression of alpha1, alpha3, alpha6 and beta4 was observed on normal ovarian epithelium with variable expression of alpha5. Loss of alpha1 expression by malignant cells in the primary tumors was noted. beta4, a component of the laminin receptor which was strongly expressed by both normal ovary and solid tumor, was absent from the ascitic tumor cells in the majority of cases. There was an associated loss of alpha6 expression, indicating a deficiency of hemidesmosomes in the ascitic tumor cells. This alteration of integrin expression by metastatic malignant epithelial ovarian tumor cells may therefore represent one important mechanism by which metastatic disease occurs.

Risk of Ovarian Cancer Is Lessened by Childbearing, Pill Use and Hysterectomy

In Ontario Canada data on reproductive history were obtained by interviews with 450 of 631 patients aged 35-79 diagnosed with primary malignant or borderline malignant epithelial ovarian tumors between November 1989 and October 1992. These data were compared with 564 age and residence-matched controls. Logistic regression analysis revealed that 1) 77% of cancer patients had given birth vs. 89% of controls; 2) that parous patients had 2.5 term pregnancies vs. 2.8 among controls; 3) that patients who ever-used oral contraceptives (OCs) used them for 4.2 vs. 5.5 years; 4) that women who had given birth were 60% less likely to develop ovarian cancer; 5) that the odds ratio decreased from 0.64 among those who had one full-term pregnancy to 0.23 among those who had 5 or more; 6) that the risk of ovarian cancer decreased 22% for each term pregnancy and that this decrease increased slightly for women with hysterectomy or a history of periods of infertility; 7) that breast feeding appeared to reduce risk; 8) that ever-users of OCs had only 50% the risk of never-users with those who used OCs for 10 or more years having a third of the risk; 9) that each successive year of OC use reduced risk by 8% among all women and among parous women and by 13% among nulliparous women; 10) that sterilization caused a small decrease in risk; 11) that hysterectomy reduced risk by about 50% and the length of time since hysterectomy did not alter this effect; and 12) that infertility is not an important factor in ovarian cancer risk. These findings confirm those reported from other studies that parity OC use and hysterectomy reduce overall ovarian cancer risk.

Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas

Intracytoplasmic mucinous inclusions and lumina have been previously described in non-glandular neoplasms such as urothelial carcinoma. We describe their presence in 93% of non-mucinous ovarian carcinomas. They were found in abundance in all 25 cases (100%) of clear cell carcinoma, in 48 of 50 cases (96%) of serous carcinoma and 20 of 25 cases (80%) of endometrioid carcinoma. The degree of the differentiation of the tumour did not influence the number of inclusions or lumina observed. These results suggest that the presence of intracytoplasmic lumina and mucinous inclusions is more widespread than hitherto appreciated. Their presence in an otherwise poorly differentiated metastatic carcinoma might, at the very last, prompt one to consider the ovary as a possible primary site. In addition, an abundance of intracytoplasmic mucinous inclusion and lumina with microcyst formation, in an otherwise poorly differentiated malignant primary ovarian epithelial tumour, might suggest the possibility of a clear cell carcinoma.

Molecular Genetic Changes Associated with Ovarian Cancer

Multiple specific chromosomal deletions can be found in human epithelial ovarian cancer by cytogenetic analysis or molecular techniques. Somatic allelic deletion or loss of heterozygosity (LOH) in a tumor is considered circumstantial evidence for the location of tumor suppressor genes. We have examined 27 primary epithelial ovarian tumors for the presence of LOH at 19 polymorphic markers on chromosomes 1, 5, 6, 9, 11, 13, and 17. Markers near the adenomatous polyposis coli (APC) gene at 5q21 showed LOH in 50% (10/20) of informative cases. LOH was seen in 53% (8/15) at the IFNA locus on 9p, another region implicated in other tumors, but not previously associated with ovarian cancer. We observed LOH for markers on 11p15 in 50% (12/24) of ovarian cancer DNAs from informative cases, while only 25% (4/16) at 11q13 and 29% (5/17) at 11q24 showed LOH. Only a portion of distal 11p was deleted in six cases. The incidence of LOH (50%) at HGH (17q22-q24) was greater than that at D17S579 (39%; 17q21), a locus tightly linked to BRCA1. Sixty-four percent (7/11) showed allelic loss at 17p11. LOH was infrequently observed at markers on chromosomes 1, 6, and 13q. Most cases showing LOH were stage III or IV, and most showed LOH at more than one locus. These studies support the concept that multiple genetic loci are involved in ovarian tumorigenesis. Two additional regions thought to harbor genes important in other cancers, 5q21 and 9p21, can now be added to the growing spectrum of molecular alterations seen in ovarian cancer.

Immunoreactive tenascin in tumours of salivary glands: evidence for enhanced expression in tumour stroma and production by tumour cells.

Tenascin, a large molecular weight extracellular glycoprotein expressed at the epithelial-mesenchymal interface during morphogenesis in embryo, wound healing and in the stroma of various benign and malignant tumours was evaluated in a series of primary epithelial tumours of salivary glands using a monoclonal antibody. Normal salivary glands (n = 5) had linear delicate band-like immunoreactive tenascin in relatively large excretory or intralobular ducts. Pleomorphic adenomas (n = 40) had heterogeneity of expression in modified myoepithelial cell-associated myxoid, hyaline and chondroid areas. Warthin's tumours (n = 10) had a linear immunoreactivity profile of tenascin just adjacent to the basal cells of the epithelial tumour component. A heterogeneity of expression with intense to low or negative stromal immunoreactivity was observed in adenoid cystic carcinomas (n = 8), mucoepidermoid carcinomas (n = 8), epithelial-myoepithelial carcinomas (n = 4), polymorphous low-grade carcinomas (n = 3), papillary cystadenocarcinomas (n = 15) and undifferentiated carcinomas (n = 3). In addition, small cystic spaces or lumens of epithelial-lined tubulo-ductal structures in numerous salivary tumours had positive immunoreactivity for tenascin, suggesting its production by the epithelial tumour component. An enhanced expression of tenascin in salivary tumours suggests a role of this protein in the stromal remodelling and tumour growth.

Human alveolar macrophage-56 and carcinoembryonic antigen monoclonal antibodies in the differential diagnosis between primary ovarian and metastatic gastrointestinal carcinomas

The immunohistochemical expression and localization of monoclonal antibodies to carcinoembryonic antigen (CEA) and human alveolar macrophage (HAM-56) were evaluated in primary ovarian and metastatic gastrointestinal (GI) carcinomas. Immunohistochemistry was performed using an avidin-biotin-peroxidase complex method with capillary gap technology on formalin-fixed, paraffin-embedded tissues from 41 primary ovarian epithelial neoplasms, 17 metastatic gastrointestinal malignancies, and 10 tumors of uncertain primary origin. Overall, immunostaining for HAM-56 was positive in 35 (85%) ovarian epithelial neoplasms compared with only two (12%) gastrointestinal cancers. Carcinoembryonic antigen was positive in 16 (39%) ovarian versus 13 (76%) GI tumors. Of the primary ovarian neoplasms, 22 were positive for HAM-56 only, 13 were positive for both HAM-56 and CEA, three were positive for CEA only (all mucinous neoplasms), and three were negative for both. Of the primary GI neoplasms, 12 were positive for CEA only (including all eight colon cancers), one was positive for both HAM-56 and CEA, one was positive for HAM-56 only, and three were negative for both. Of the 10 neoplasms of unknown origin at initial presentation, six were positive for HAM-56 only, three were positive for CEA only, none was positive for both HAM-56 and CEA, and one was negative for both. Only three of these 10 neoplasms remained of indeterminate origin after pathological review and clinical follow-up. When positive, CEA was usually strong and generalized in GI cancers but weak and focal in ovarian neoplasms. The HAM-56 positivity in ovarian neoplasms was typically focal and largely limited to areas with glandular or papillary differentiation with apical linear accentuation. We conclude that an immunohistochemical panel using both HAM-56 (Enzo Diagnostics, Syosset, NY) and CEA monoclonal antibodies is helpful in differentiating primary ovarian neoplasms from metastatic gastrointestinal malignancies, and in evaluating metastatic adenocarcinoma of unknown primary site.

Epithelial tumors of the lacrimal gland

The clinical features of 30 primary epithelial lacrimal gland tumors encountered during a 30-year-period are discussed. Fourteen patients (46.6%) had pleomorphic adenomas, twelve (40%) had adenoid cystic carcinoma, two (6.7%) had pleomorphic adenocarcinoma and two (6.7%) had mucoepidermoid carcinoma. Patients with malignant tumors usually had a short history of a few months with pain while pleomorphic adenoma cases had a longer history without pain. Pleomorphic adenomas generally caused enlargement of bone but there was bone erosion in two cases. Malignant tumors were radiologically normal or there was bone expansion or destructive changes. Chronic dacryoadenitis was found to closely masquerade both the benign and malignant lacrimal gland tumors. An en bloc excisional biopsy is necessary in pleomorphic adenomas while an extraperiosteal approach should not be used in malignant tumors.

Head and neck cancer prevention: the new challenge.

M ULTIPLE approaches of treatment, including neoadjuvant chemotherapy, for patients with squamous cell carcinoma (SCC) of the head and neck have produced a significant number of encouraging response rates, but they have not improved overall survival. The standard treatment for patients with SCC of the head and neck has been local therapy with surgery and/or irradiation. Chemotherapy with 5-flourouracil and cisplatin has been reserved for patients with large recurrent or second primary disease. The response rates with this regimen have been between 40% and 89%, with complete response rates between 4% and 20% in prospective randomized trials. 1 Head and neck cancer accounts for approximately 5% to 6% of all cancers in the United States. Head and neck cancer is directly associated with tobacco, and in the United States, 50 million people smoke cigarettes and 12 million chew tobacco, Worldwide, the corresponding figures are 1 billion and 600 million, z Despite the large number of smokers in the United States, the 1993 estimated incidence of head and neck cancer is 32,000 and the estimated mortality is 8000. 3 Hsu et al 4 investigated the response of cells of line 3640P by adding 2% and 4% alcohol to two of their three separate mediums and found that the 4% alcohol practically shut off DNA synthesis. The apparent conclusion is that alcohol actually exerts a toxic effect on DNA synthesis, thus creating a vulnerable cellular environment towards invasion of carcinogens. They also reported that concomitant smoking and alcohol appears to increase the risk of developing head and neck cancer. It was found in a study that the interaction between alcohol and tobacco smoke were such that they enhanced the genotoxicity of each other and a dose-response relationship between these two cocarcinogens increases the risk of development of head and neck cancer by 44.5%. 5 Sun exposure also contributes to the risk of squamous cell head and neck cancer. Choy et al 6 studied squamous cell cancer of the head and neck in Chinese patients from Hong Kong and they determined that they had a 10% to 14% risk of multiple primary cancer (MPC). Second primaries were reported in 1% to 35% of these patients. According to a study by Robinson eta/ , 7 the mean age of patients developing a first primary tumor was 61 years and the mean age of those developing a second primary tumor was 64 years. The study showed that out of 638 patients, males had a greater incidence than females, and whites developed the disease more than nonwhites. Kotwall et al,s reported that 150 of 832 patients with head and neck cancer showed evidence of MPC's at the time of autopsy, with an overall incidence of 18%. Patients with cancers of the oropharynx and the hypopharynx had the highest incidence of MPCs. A review of oral cancers by Garewal and Meyskens 9 indicated that even after successful primary therapy of early-stage or locally advanced tumors, 30% to 50% of patients experienced local or regional recurrence, 20% to 30% had distant metastasis, and 10% to 40% had a second primary tumor. Second primary tumors affect the overall outcome of the patient with head and neck cancers and are the chief cause of treatment failure and death in those who present with early-stage disease. The reason for this increased incidence is probably related to the concept of field cancerization (diffuse mucosal membrane initiation and promotion), whereby exogenous factors such as tobacco and alcohol may serve as tumor promoters in the development of second primary epithelial tumors in the upper aerodigestive tract. The exogenous factors begin to change and destroy the epithelial portion of the soft tissues early, creating a lifetime environment of carcinogenic exposure. This exposure destroys the mechanisms of DNA and RNA replication, preventing regeneration of healthy tissues. Scientists believe that genetic and/or environ-

Molecular genetic changes in human epithelial ovarian malignancies

The frequent finding of loss of heterozygosity (LOH) for a specific chromosomal marker in tumor DNA compared to normal DNA suggests the presence of a closely linked tumor-suppressor gene. Using Southern blot analysis, 34 primary ovarian epithelial tumors were examined for the presence of tumor-specific allelic losses, using six probes for chromosomes 6q, 11p, 13q, 16q, and 17p. A high incidence of LOH was observed on 11p, 13q, and 17p. LOH for 17p was present in 3 of 4 (75%) informative benign ovarian tumors, 1 of 5 (20%) borderline tumors, and 16 of 24 (67%) invasive ovarian cancers. Allelic loss with the H-ras1 probe on 11p was present in 10 of 19 (53%) invasive tumors but was not identified in 6 benign or borderline tumors. LOH on 13q was present in 18 of 31 (58%) informative cases including 8 of 10 (80%) Stage 1 tumors. This preliminary study suggests that loss of tumor-suppressor genes on chromosomes 13q and 17p may be early events in ovarian tumorigenesis and that changes on chromosome 11p are later events.

Tumours of the spermatic cord and paratesticular tissue. A clinicopathological study.

A total of 85 patients with paratesticular tumours were diagnosed over a period of 36 years at this hospital; 66 patients (78%) had benign tumours, usually either an adenomatoid tumour or a lipoma. Of the remaining 19 malignant cases, 10 were primary neoplasms and 9 were metastases. A rare mucin-secreting epididymal adenocarcinoma was the only primary malignant epithelial tumour, the others being of mesenchymal origin. In 4/9 metastatic cases the initial presentation of a paratesticular swelling led to the discovery of the occult primary neoplasm following histological examination. Clinical features of a painful or painless mass, with or without an accompanying hydrocele, do not help to distinguish a benign from a malignant lesion. The prognosis of malignant tumours of mesenchymal origin depends mainly on the histological grade. Surgical resection remains the mainstay of treatment and adjuvant therapy significantly improves the chances of survival only in young patients with paratesticular rhabdomyosarcomas. Older patients with high grade tumours usually succumb to their disease despite chemotherapy and/or radiotherapy.

Human Papillomavirus in Primary Epithelial Tumors of the Lacrunal Sac

The lacrimal sac epithelium can give rise to benign and malignant neoplasms. Human papillomavirus (HPV) infection is known to be causal in the development of epithelial neoplasias elsewhere in the body. The authors have examined primary lacrimal sac tumors for the presence of HPV. Nine primary lacrimal sac tumors (3 benign papillomas and 6 carcinomas) submitted to the Eye Pathology Laboratories at the Wilmer Institute between 1960 and 1991 were examined for the presence of HPV sequences by in situ hybridization and the polymerase chain reaction (PCR). Of the nine tumors, only six were suitable for analysis by PCR or in situ hybridization. All three papillomas were positive for HPV type 11. Three of the carcinomas were positive for HPV sequences, and one case could be further characterized as HPV type 18. Human papillomaviruses appear to be involved in the genesis of both benign and malignant neoplasms of the lacrimal sac epithelium. As in the genital tract, HPV type 11 is associated with benign lesions, whereas HPV type 18 is associated with malignancy.

M-CSF (monocyte colony stimulating factor) and M-CSF receptor expression by breast tumour cells: M-CSF mediated recruitment of tumour infiltrating monocytes?

Infiltrating immune cells in 30 primary human epithelial breast tumours were studied using specific anti-CD3 (T cells), anti-CD68 (macrophages), anti-CD57 (NK cells), and an anti-pan-B cell antibody (L26). The majority of tumour infiltrating inflammatory cells are T cells (40-50%) and monocytes/macrophages (15-35%). The macrophage specific chemo-attractant and growth factor CSF-1 is detected by immunohistochemical techniques (IHC) at the level of invasive breast cancer cells in 46/50 tumours but not at the level of in-situ (pre-invasive) cancer. A mosaic staining pattern was usually observed, with a very high expression in areas of obvious stromal invasion (90% cells positive) and absent or trace staining in intraductal carcinoma. Macrophages and plasma cells are equally intensely positive. In-situ hybridisation experiments confirm the production of CSF-1 (mRNA) by tumour cells and show the same pattern of expression. Expression of the CSF-1 receptor protein (fms) was also observed by IHC in 41/48 invasive tumours, albeit at weaker intensities than in tumour infiltrating monocytes/macrophages. A concomitant expression of both CSF-1 and fms in in-situ carcinoma was never seen (n = 14). It is therefore proposed that the associated expression of CSF-1 and its receptor may be linked to the invasive potential of breast cancer, the monocytic infiltrate being an indication of the quantitative importance of CSF-1 production by the tumour.