Adenocarcinoma of the ileoanal pouch for ulcerative colitis--a complication of severe chronic atrophic pouchitis?

BACKGROUND: The appearance of a carcinoma in the ileal pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative proctocolitis is rare. Most of these adenocarcinomas previously described in literature develop from residual viable rectal mucosa. We report a case of an adenocarcinoma arising in all probability from the ileal pouch after malignant transformation of the ileal pouch mucosa based on a chronic atrophic pouchitis. PATIENT AND METHODS: A 34-year-old man developed an adenocarcinoma after a double-stapled ileorectal J-pouch for ulcerative colitis (UC) proceeded from malignant ileal transformation. Before surgery, he had a 20-year history of UC refractory to medical therapy, but no occurrence of backwash ileitis, dysplasia or colitis-associated illness. He experienced severe pouchitis after IPAA since the ileostomy closure. Carcinoma was ensured by endoscopy, and the patient underwent an abdominoperineal pouch extirpation combined with excision of perirectal tissues and anal canal. Histology after surgery showed a pT4,pN2(4/16)pM0,G3 adenocarcinoma with global severe chronic atrophic pouchitis (CAP), villous atrophy and malignant ileal transformation. No metaplasia of the rectal mucosa was found, not even malignant epithelial transformation of the anal canal. CONCLUSION: This case suggests that a malignant transformation of the ileal pouch mucosa may occur as a pure complication of severe CAP, even in the absence of backwash ileitis or a previous history of cancer. The absence of metaplasia of the rectal mucosa revealed the passage from CAP to dysplastic epithelium and to cancer. A multifactorial development of carcinogenesis is supposed, but we emphasize the importance of severe CAP, and that careful surveillance is needed in patients after IPAA. We must submit that this is just a case report and cannot stand for general cancer development in ulcerative colitis, but it may point out the risk factor of chronic inflammation and leads the surgeon to skillful working when building the pouch.

Smooth muscle tumours of the uterine corpus: a clinicopathologic study with immunohistochemical aspects.

BACKGROUND: Based on a clinicopathologic study conducted at the University of Rostock, Germany, between 1/1997 and 6/2003, the histological records of 1761 patients who had been hysterectomized were evaluated. 1422 of these patients were suffering from smooth muscle tumours: 1389 were diagnosed as multiple leiomyomas, 26 as leiomyomas of uncertain malignant potential and 7 as leiomyosarcomas. PATIENTS AND METHODS: The data about the microscopic findings were obtained by use of both conventional histology (HE and Giemsa) and immunohistochemistry with markers for leiomyosarcomas (desmin, actin, sm-actin, myoglobin, vimentin, MIB1) and evaluated by statistical methods. Three case reports are also presented: 2 patients with leiomyosarcoma and 1 patient with an UMP tumour. RESULTS: The statistical evaluation included the frequencies of the different tumours subdivided into age groups, their localizations (with 23 distinctions), the associated microscopic findings (with 12 distinctions and most important combinations) and, finally, the number of tumours per patient and their (grouped) sizes. The case reports showed the presence of nuclear atypia, a heightened mitotic index and tumour cell necrosis. Immunohistochemical methods confirmed the histological diagnosis of a leiomyosarcoma. CONCLUSION: In accordance with earlier studies, more than 95% of the smooth muscle tumours were leiomyomas. Leiomyosarcomas were rare (<1% in our study). In 3 out of 7 cases, a leiomyosarcoma had its origin in a leiomyoma.

[Contraction of the hip and fecal drainage via a fistula tract 30 years after "appendectomy"]. / Stuhlfistel und Hüftgelenkskontraktur 30 Jahre nach "Blinddarmoperation".

A 46-year-old female was admitted with increasing fecal drainage via a fistula tract in the right inguinal region. She had a history of surgery for appendicitis 30 years previously, from which there was disturbed wound healing resulting in a blunt fistula, and the patient suffered from contraction of the right hip. Computed tomographic scan and ultrasound demonstrated an inflammatory mass in the right inguinal region. Colonoscopy demonstrated a stenosis of the rectosigmoid junction but did not provide any further specific information. Surgery revealed the presumed diagnosis of complicated Crohn's disease, but an advanced squamous cell carcinoma was also identified. The patient died 23 months later due to generalized tumor. Although malignant transformation of a fistula tract is rare, this case demonstrates that long-standing fistulas should be cured as far as possible without significant morbidity. In the case of incurable fistulas, malignancy must definitely be excluded if the clinical appearance of the fistula changes.

[Stapes fixation in children]. / Stapesfixation bei Kindern.

BACKGROUND AND OBJECTIVE: The audiometric results after stapes surgery in children with isolated stapes footplate fixation were reason enough to analyze intraoperative findings and surgical procedures. PATIENTS/METHODS: A total of 438 stapes surgeries were performed in the years 1985-2000, and a retrospective analysis was made of the anamnestic data, intraoperative findings and audiometric data from 12 children with isolated fixation of the stapes footplate. The average age of the children when operated was 10.2 years (the youngest was 7 and the eldest 13). A loss of hearing had set in 5 years earlier. RESULTS: Taking the anamnestic data and the intraoperative into account, otosclerosis was found in 5 children. One child had a narrow oval window niche, in a further six children a congenital fixation of the stapes footplate was evident. Only 58% (n=7) of the 12 children operated showed acceptable postoperative hearing results. The best hearing results were found in children with juvenile otosclerosis. In three of six children with congenital stapes fixation, a worsening of both bone and air conduction was evident. The average conductive hearing loss was 30 dB at 1, 2 and 4 kHz. CONCLUSIONS: When explorative tympanotomy is indicated, a thin-layer CT scan of the temporal bone should be made to assess the risk of a liquor pressure labyrinth developing.

Cytology and image cytometry after colonic lavage: a complementary diagnostic tool in patients with ulcerative colitis.

BACKGROUND: Patients with extensive, long-standing ulcerative colitis have increased risk of colorectal cancer. AIMS: To improve the detection of high-risk patients, using a combination of colonic cytology, histology, and DNA image cytometry after segmental colonic lavage. PATIENTS: A series of 16 patients (8 high-risk patients) with ulcerative colitis were investigated. METHODS: After segmental lavage step, biopsies were obtained. Gradient centrifugation of the colonic fluid was performed for isolation and purification of epithelial cells. The smears and biopsy specimens obtained were stained for routine interpretation and for DNA image cytometry. RESULTS: Segmental lavage could be performed in all patients. Specimens from two high-risk patients showed low grade dysplasia and atypia by means of histology and cytology, respectively. In one patient, without increased colorectal cancer risk, atypia was detected. Three patients in the high-risk group, two of those diagnosed as positive for dysplasia and atypia, showed aneuploidy histologically and cytologically. DNA aneuploidy, in cytological material, was found exclusively in three low-risk patients, one of those had atypia cytologically. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage using density gradient centrifugation can be performed as part of routine endoscopy. It provides information about atypical cells and DNA aneuploidy as additional markers of malignant transformation. The combination of cytologic examination and DNA image cytometry might improve the detection of high-risk ulcerative colitis patients.

[Frozen section telepathology in the clinical routine of a breast cancer center]. / Schnellschnitttelepathologie im klinischen Alltag eines Brustzentrums.

For an intraoperative frozen section service, the period from surgeon's sample excision to the time of transmitting the diagnosis by the pathologist, should not last longer than 20 min. In a period of 16 months we performed 389 frozen sections by telepathology (298 patients) in our breast cancer center, using the Leica telepathology system (TPS 1.5). In 173 out of the 389 sections, an invasive carcinoma was diagnosed (312 frozen sections with the aim to verify malignancy and 77 to verify a tumor-free retroareolar resection margin). The overall error rate amounted to 7 out of 389 sections (about 2%; false-negative in 5 cases, false-positive in 2 cases) and is equivalent to the error rate without telepathology. The mean time for diagnosis per case was 15 min. For the future, it is desirable that hospitals without their own pathologists also perform frozen sections within an adequate time by using telepathology systems.

[An intraosseous hemangioma in the perpendicular lamina of the ethmoid bone]. / Intraossäres Hämangiom der Lamina perpendicularis ossis ethmoidalis.

The incidence of intraosseous hemangiomas is very low. Most of them occur in adult females. The mandible,the zygoma,the maxilla, and the frontal and nasal bones are the areas of most frequent localization in the facial region. The intraosseous hemangioma is a benign, slowly growing,bony hard tumor causing facial deformity. It is diagnosed histologically. We report a case of an 18-year-old male with an intraosseous cavernous hemangioma located in the perpendicular lamina of the ethmoid bone. Intraosseous hemangioma often has characteristic signs on a CT scan, with either coarsened trabeculae lying adjacent to the vascular channels or multifocal lytic areas creating a honeycomb pattern. Because of the age of the patient we considered a midline granuloma and a chondrosarcoma. The therapy of choice is surgical excision; radiation is done in exceptional cases only.

Fluorescence endoscopy using a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen in patients with colorectal carcinoma and adenoma.

BACKGROUND AND STUDY AIMS: Various methods of fluorescence excitation and detection have been developed in gastrointestinal endoscopy. This study reports an endoscopic technique using locally applied fluorescein-labeled antibodies for in-vivo detection of colorectal dysplasia and carcinoma. PATIENTS AND METHODS: Fluorescence endoscopy with a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen (CEA) was carried out in 27 patients with colonic polypoid lesions. During conventional colonoscopy, the monoclonal antibody was applied directly onto the mucosal surface. After an incubation time of 10 min, specific fluorescence was visualized with a conventional endoscope whose optical range was increased via two narrow-band filters. RESULTS: Fluorescence in vivo was present in 19 out of 25 carcinomas and in three of eight adenomas. The technique failed in the presence of mucosal ulceration or bleeding. One fluorescence-positive villous adenoma showed high-grade dysplasia, and another fluorescence-positive polypoid lesion was diagnosed as carcinoma in adenoma. Normal-appearing mucosa was fluorescence-negative in all cases. Endoscopic fluorescence significantly correlated with the CEA expression of luminal epithelial cells as determined immunohistochemically (Wilcoxon-Mann-Whitney U-test, P < 0.01). In all cases without ulceration or bleeding, the specificity of fluorescence endoscopy was 100%, the sensitivity was 78.6%, and the accuracy was 89.3%. CONCLUSIONS: Fluorescence endoscopy using fluorescein-labeled monoclonal antibody against CEA was shown to be positive in most cancers and some adenomas. Further and larger studies will be needed to demonstrate the value of this technique for differential diagnosis.

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease.

Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis.

Distal chromosome 17 gains in neuroblastomas detected by comparative genomic hybridization (CGH) are associated with a poor clinical outcome.

PROCEDURE: To establish the significance of chromosome 17 aberrations in the biology of neuroblastomas, the fresh-frozen material of 53 primary neuroblastomas (average patient age: 20.8 months; stage 1 or 2: n = 10; stage 3: n = 10; stage 4: n = 10; stage 4s: n = 23) was studied by means of comparative genomic hybridization (CGH). Follow-up data were available for 52 of 53 cases studied (average follow-up period: 26.4 months). Except for one, all cases had previously been analyzed for MYCN status (semiquantitative Southern blot analysis). Studies of LOH 1p36 (VNTR-PCR) had been performed on 28 of 53 cases. RESULTS: Chromosome 17 gains were detected in 46 of 53 (86.8%) cases. Whole chromosome gains were mostly restricted to localized tumors (stage 1 or 2: 9 of 10 cases; stage 4s:19 of 23; stage 3: 2 of 10; stage 4:0 of 10 cases), whereas distal 17 gains were significantly associated with clinically advanced tumor stages and patients aged over 1 year at diagnosis. Univariate analyses revealed a statistically significant correlation of distal 17q gains with overall survival (P< 0.01, MYCN amplification: P< 0.01; 1p deletion: P< 0.01) and an elevated recurrency rate (17q: P= 0.02, MYCN amplification: P = 0.05; 1p deletion P= 0.3). There was a strong coincidence of distal 17q gains and 1p deletion or MYCN amplification (P < 0.01). CONCLUSION: Our data indicate that distal chromosome 17q gains are of major prognostic relevance for neuroblastoma patients. However, studies on a larger series of tumors have to be performed to assess whether or not these alterations are independent prognostic markers of a poor clinical outcome.

Diagnostic value of DNA image cytometry in ulcerative colitis.

The increased risk of colorectal cancer in patients with extensive, long-standing ulcerative colitis is well established. The interpretation of dysplasia as the common precursor lesion of colorectal cancer in ulcerative colitis is, however, subject to inter- and intraobserver variation. The histologic diagnosis is particularly difficult in the presence of acute inflammation. Therefore, the analysis of ploidy patterns might be a more objective diagnostic tool. In the present study, the correlation of ploidy and dysplasia of the colonic mucosa was evaluated in the absence and presence of inflammation. Image cytometry was performed on 561 fixed, paraffin-embedded tissue specimens from 67 patients with ulcerative colitis. Twenty patients had long-standing and extensive disease, including eight patients in whom the colitis was associated with colorectal cancer. Dysplasia was only found in patients with long-standing colitis or with colorectal cancer and was significantly more often diagnosed in the case of concomitant inflammation. On the other hand, aneuploid patterns were shown to occur independent of inflammatory activity. Aneuploidy was present in all colorectal carcinomas associated with ulcerative colitis and in 46.2% of specimens with dysplasia. Moreover, aneuploidy was detectable in four of 12 samples with low-grade dysplasia as well as in one case devoid of any dysplastic alteration. Ulcerative colitis patients with low-grade dysplasia plus aneuploidy probably represent a subgroup that might be at higher risk of developing colorectal cancer than patients with low-grade dysplasia alone. All in all, image cytometry analysis might be instrumental in identifying neoplastic lesions even in cases of increased inflammatory activity or regenerative change.

Cytogenetic analysis of multifocal bladder cancer supports a monoclonal origin and intraepithelial spread of tumor cells.

Bladder cancer is often characterized by a multifocal growth pattern. This observation has given rise to the hypothesis of "field cancerization," predicting a polyclonal origin of multiple tumors rising from an area of independently transformed mucosa cells. On the other hand, genetic studies suggested a monoclonal origin. To address these contradictory hypotheses, we performed comparative genomic hybridization (CGH) on 32 tumors originating from six bladder cystectomy specimens. All tumors derived from the same patient showed a set of 7-13 identical chromosomal aberrations and additional individual alterations. Most striking were the findings of 17p losses in all (32 of 32) tumors of the six cystectomy specimens and 20p gains in all tumors of four bladders, as well as an unexpected high number of chromosomal changes (20.4 alterations per tumor on average). To clarify a possible role of the TP53 tumor suppressor gene on 17p13, we applied immunohistochemistry and sequence analysis on the tumors and additional 52 mucosa samples. Identical TP53 mutations and protein overexpression was found in individual tumors only as well as in mucosa samples from continuous areas. Our results not only provide further evidence for a monoclonal origin of multifocal bladder cancer but also point at intraepithelial migration of tumor cells carrying specific chromosomal aberrations.

Patterns of chromosomal imbalances in muscle invasive bladder cancer.

Cytogenetic investigations of bladder cancer suggested that development and progression is characterized by specific chromosomal aberrations. In order to identify genetic changes linked to muscle invasive tumors and metastatic growth we analyzed 67 bladder carcinomas (30 pT1 and 37 pT2-4) by means of comparative genomic hybridization (CGH). The most frequent changes were gains of chromosome 1q (54%), 8q (54%), 17q (49%), 2p (30%), 12 (30%), 5p (25%), 3q (24%) and 6p (24%) as well as losses of 11p (43%), 8p (42%), 9p (36%), 11q (34%), 2q, 4q, 5q (30% each), 9q (27%) and 10q (27%). Previously not described amplifications were found at 5p11-p13, 7q21-q31, 9p24 and 17q24-q25. Gains of 3q, 7p, and 18p were markedly more frequent in pT2-4 in comparison to pT1 carcinomas but the difference did not reach statistical significance. Non-metastatic tumors showed more aberrations on average than metastatic carcinomas, although no particular change was found to be predominating in either group. Our data confirm previous findings of strong genetic similarities between minimally and deeply invasive bladder carcinomas but argue for differences between metastatic and non-metastatic disease.

CD44s, E-cadherin and PCNA as markers for progression in renal cell carcinoma.

CD44s, E-cadherin and PCNA play an important role in the tumorigenesis of renal cell carcinoma (RCC), although their significance in the clinical progression of RCC is still not clear. In n = 137 cases of operatively resected RCC the expression of CD44s, E-cadherin and PCNA was semiquantitatively analyzed by the APAAP immunohistochemical method. The mean observation period of the n = 74 (54%) of patients with no evidence of disease was 52.6 months and for the n = 63 (46%) patients with progressive disease was 18.7 months. The mean progression free period occurring with absent or low levels of CD44s and PCNA expression was 79 and 118+ months, and with strong expression was 12 and 18 months (p < 0.001), respectively. With strong E-cadherin expression the progression free period was 110+ months, and with low expression 61 months (p = 0.01). A high CD44s/E-cadherin ratio and an above average PCNA expression were identified as independent prognostic parameters for the progression tendency of RCC.

Immunophenotypic and prognostic analysis of E-cadherin and beta-catenin expression during breast carcinogenesis and tumour progression: a comparative study with CD44.

AIMS: This study was performed to investigate whether immunohistochemical expression of E-cadherin (E-cad) and beta-catenin (beta-cat) in conjunction with CD44 may correlate with the clinical evolution and prognosis of breast cancer. METHODS AND RESULTS: One-hundred and forty-two routinely processed breast tissue samples including normal breast, benign lesions, in situ and invasive carcinomas were investigated. E-cad and beta-cat were strongly expressed by luminal and basal cells in normal glands, benign proliferative and early neoplastic intraductal lesions. Contrarily, CD44 was expressed exclusively by myoepithelial cells in normal breast, whereas different isoform expression patterns were observed in premalignant and malignant lesions. Simultaneous lack of E-cad/beta-cat expression was detected in in situ and invasive lobular carcinomas in contrast to ductal lesions, in which the differential loss of the molecules was associated with poorer differentiation, irrespective of CD44 immunophenotype. Reduced E-cad (P = 0.003), beta-cat (P = 0.03) and increased CD44v4 (P = 0.005) and v7 (P = 0.007) expression were significantly associated with positive lymph node status. Decreased E-cad and lack of CD44v6 expression correlated with poor survival. There was no difference between the expression of either molecule in in situ and invasive components within the same tumour. CONCLUSIONS: Our results indicate that changes in E-cad, beta-cat and CD44 expression occur early in breast carcinogenesis; they are involved in tumour differentiation, but events additional to their deranged expression are needed to acquire an invasive phenotype.

Density gradient centrifugation of colonic fluid after segmental lavage: a method of purification of exfoliative epithelial colonic cells for cytological interpretation and image cytometry in patients with long-standing ulcerative colitis.

OBJECTIVES: Patients with extensive, long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer. In this study, we wanted to establish a method for retrieving cytological material after segmental colonic lavage for further cytopathological investigations and for performing DNA image cytometry. METHODS: Ten patients with long-standing and extensive ulcerative colitis and 10 patients without macroscopic abnormalities were investigated. After segmental colonic lavage during routine colonoscopy a three-layer (1.146, 1.075, and 1.046 g/ml, respectively) density gradient centrifugation of the retrieved colonic fluid was performed for isolation and purification of the epithelial cells. For identification of the epithelial cells flow cytometry with monoclonal antibody against cytokeratin and counterstaining with propidium iodine was performed. The smears obtained were stained for routine cytopathological interpretation and for DNA image cytometry. RESULTS: In eight of 10 UC patients and in nine of 10 control group patients adequate cytological material could be obtained. The band on top of the density gradient at 1.046 g/ml could be identified as the epithelial cells. Atypical cells were found in smears of three UC patients. In these patients and in one additional patient aneuploid stemlines could be detected. In smears of control group patients neither atypical cells nor aneuploidy were present. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage by using density gradient centrifugation was performed. This cytological material is adequate for cytopathological interpretation and for DNA image cytometry. Information about atypical cells and DNA aneuploidy as an additional marker of malignant transformation in UC patients was obtained. The combination of cytological examination and DNA image cytometry might improve the detection of UC patients with high risk for colorectal cancer.

Prognostic importance of the expression of CD44 splice variants in oral squamous cell carcinomas.

Considering squamous cell carcinomas (SCCs) of the oral cavity and oropharynx the molecular mechanisms underlying the infiltration and destruction of adjacent tissue as well as the metastatic spread are largely unknown. In this context, the detection of defective expression of cellular adhesion molecules in the tumour cells, e.g. CD44, might be important and correlated with prognosis. Paraffin-embedded tumour-tissue from 99 patients with primary oral and oropharyngeal SCC, additionally including corresponding lymph-node metastases in nine cases, was analysed for expression of the CD44 splice variants v4, v5, v6, v7, and v9 by means of immunohistochemistry. A diminution of at least one of the examined CD44 isoforms compared to the normal oral epithelium was observed in 39.4% of the squamous cell carcinomas. No correlations could be found between CD44 expression and pT- or pN-stage. However, decreased expression of v9 was correlated with higher histological grade (p < 0.001). Moreover, reduced CD44 expression was a statistically significant independent predictor for shorter survival time (p = 0.002) as well as shorter recurrence-free interval (p = 0.004) in addition to pT- and pN-stage. The separate analysis showed that particularly the decreased v7 (p = 0.04) and v9 (p < 0.02) expression in the tumour cells was associated negatively with survival.

Chromosomal aberrations associated with invasion in papillary superficial bladder cancer.

Non-invasive and invasive papillary transitional cell carcinomas of stages pTa and pT1 represent the first steps of tumour progression in bladder cancer. In order to analyse different chromosomal alterations of pTa and pT1 superficial bladder cancer, 46 tumour specimens were examined by comparative genomic hybridization (CGH). Losses of chromosome 9 material (11/20) and gains of chromosome 17 material (6/20) were frequently found in pTa tumours. Stage pT1 tumours were characterized by gains of chromosome 1q (14/26; including amplification at 1q21-q24 in three cases) and chromosome 17 material (15/26), as well as by losses of 11p (15/26) and 11q (13/26). Other loci frequently showing losses in pT1 tumours were 2q (9/26), 4q (10/26), 5q (9/26), 8p (10/26), 9p (9/26), 9q (12/26), 10q (8/26), 17p (7/26), and 18q (8/26). Amplifications were detected at 8q21/22, 5q21, 7q36, 10p14, 10p12, 10q25, 12q12, and 12q14. The most striking differences between grade 2 pTa and pT1 tumours were gains of 1q (P < 0.01) and losses at 2q (P < 0.025), 10q (P < 0.05), 11p (P < 0.01), 11q (P < 0.01), and 17p (P < 0.05), as well as the total number of aberrations (pTa grade 2: 4.1; pT1 grade 2: 8.6 aberrations per tumour). These data show characteristic chromosomal aberrations associated with invasion in superficial bladder cancer.

Gains and losses of CD44 expression during breast carcinogenesis and tumour progression.

AIMS: This study was performed to investigate whether the CD44 immunophenotype of breast lesions correlates with the clinical evolution and prognosis of breast cancer. METHODS AND RESULTS: One-hundred and fifty-two routinely processed normal, benign and malignant breast tissue samples were investigated by the following monoclonal antibodies: CD44s (F10-44-2), CD44v3 (3G5), CD44v4 (11.10), CD44v5 (VFF-8), CD44v6 (VFF-18), CD44v7 (VFF-9), CD44v9 (11-24) after wet autoclave pretreatment for antigen retrieval. We found that: (1) in normal breast tissues luminal epithelial cells lacked detectable CD44 in contrast to basal cells, which constitutionally expressed CD44s, v3, v5 v6 and v9 isoforms; (2) in the intraductal compartment of benign hyperplastic lesions, there was scattered or focal staining for CD44s, v5, v6, v7 and v9 isoforms; (3) in neoplastic lesions restricted neo-expression of CD44v3 and v4 was detected; and (4) the CD44 immunophenotype of invasive breast carcinomas was influenced largely by differentiation grade, steroid receptor status of the tumours and significantly correlated with metastatic involvement of the axillary lymph nodes. CONCLUSIONS: Qualitative and quantitative changes of CD44 expression are implicated in early stages of breast carcinogenesis. The restricted neo-expression of certain CD44 isoforms in breast neoplasias suggests that CD44 might be a potential target for future antibody-based tumour therapy.