CD44 isoforms with exon v6 and metastasis of primary N0M0 breast carcinomas.

New isoforms of CD44 with alternatively spliced exons have recently been described. Expression of exon v6 seems to be of particular interest. It has indeed been associated with poorer outcome of breast cancer patients with node invasion at diagnosis. However, no data were available for patients N0M0 (with neither metastasis nor node invasion at diagnosis). Moreover, previous statistical analyses were realized using immunohistochemical methods to detect CD44v6 expression although several variants with exon v6 have been described. We investigated expression of isoforms containing CD44v6 using an RT-PCR approach and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic samples and 52 primary breast tumors (38 invasive N0M0). Normal breasts, fibroadenomas, and cysts all express the same variant, A (with exon v6 only), while several transcripts are amplified in tumors. Expression of variants other than A correlates with acquisition of a malignant phenotype. Invasive cancers also express additional variants in comparison with in situ carcinomas. Metastasis capacities seem to be associated with transcription of variants other than A but also with no transcription of some of them, variants D (with exons v6 and v10) and L (with exons v6 to v10). Expression of variants D and L correlates with higher percentages of disease-free survival and better outcome. Expression of CD44 splice variants with exon v6, as detected by RT-PCR, might be a useful prognostic factor for breast cancer. However, since the series size is small, our results need to be confirmed by later studies on a larger number of patients.

Expression of CD44 spliced variants with both exons v9 and v10 in primary N(-)M(-) breast carcinomas correlates with metastasis.

We analyzed the representation of CD44 isoforms with both exons v9 and v10 among CD44 total amount and also examined correlation between their expression, clinical parameters and survival. We used a semi-quantitative RT-PCR reaction and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic samples and 52 primary breast tumors. CD44 expression level was statistically higher in malignant tumors than in normal breast tissues (p = 0.038) or in fibroadenomas (p = 0.047) and correlated with histological grading, p = 0.047. Ratios CD44 variants with both exons v9 and v10/ total CD44 were similar in normal breast tissues and fibroadenomas but lower in the cystic samples. In primary N(-)M(-) breast tumors, unfavourable outcome and relapse were correlated with low ratios.

Are CD44 spliced variants involved in human breast cancer metastasis?

Expression of CD44 isoforms has been investigated on normal breasts, fibroadenomas, cysts and breast cancers. Carcinomas express additional variants in comparison with normal breasts while fibroadenomas and cysts do not. Invasive cancers also express more variants than in situ carcinomas. Recent studies tend to demonstrate that overexpression of CD44 is not a survival prognostic factor whereas expression of exon 2v and/or 3v could be. Results for exons 4v to 10v are presently conflicting. Further studies will then be necessary to clarify the role of CD44 isoforms in mammary carcinogenesis and metastasis. Metastatic capacity could be linked with expression of additional variants but also with no transcription of variants associating exon 6v with either exon 10v or both exons 9 and 10v.

CD44 exon 6 expression as a possible early prognostic factor in primary node negative breast carcinoma.

Breast cancer is the most common female malignancy affecting approximately one woman in eight. Many attempts have been made to define markers which may have potential clinical applications in diagnosis as well as therapy. New isoforms of CD44 with alternative spliced exons have recently been described. We studied the expression of CD44 exon 6 using a semi-quantitative RT-PCR reaction on a panel of 25 normal breast specimens, 10 mammary fibroadenomas, eight cystic samples and 52 primary breast tumors. Significant correlation was found between CD44 exon 6 expression and the overall survival of the N-M-population, P = 0.032, (logrank test by Mantel's method). The same result was also observed for the disease-free survival, P = 0.000002 (logrank test by Mantel's method). CD44 exon 6 expression, as detected by our RT-PCR-based method, might be a useful prognostic indicator of metastasis in breast cancer. However, these preliminary results need to be confirmed by later retrospective and prospective studies on a larger number of patients.

E-cadherin mRNA expression in breast carcinomas correlates with overall and disease-free survival.

E-cadherin (Epithelial-cadherin) is a subclass of the cadherin family that plays a major role in the maintenance of intercellular junctions in epithelial tissues. E-cadherin is also involved in the interactions between epithelial cells and T lymphocytes. In order to explore the relationship between E-cadherin expression, cancer invasion and metastases in vivo, we estimated its expression in normal breast specimens, fibroadenomas, cystic samples and primary breast carcinomas using a semiquantitative reverse transcription-polymerase chain reaction. The relationship between E-cadherin expression, survival and disease-free survival was also investigated. In comparison with normal breasts, 70% of the primary tumors showed reduced expression of E-cadherin suggesting that downregulation of this cell adhesion molecule is a common event in breast carcinoma. Significant correlation was found between E-cadherin expression and the histological classification. Most of the advanced tumors grades (10/13 tumors with grade III) presented decreased E-cadherin expression. No correlation was found between E-cadherin expression, estrogen and progesteron receptors, age and menopausal status at diagnosis. However, disease-free and overall survival was associated with E-cadherin expression. Patients showing poorly expressed E-cadherin in tumor tissue had a worse prognosis. The same results were observed for women without lymph node invasion or metastasis at diagnosis even when they were grouped according to their histological grade for statistical analysis. Therefore, E-cadherin mRNA expression in invasive breast carcinomas might be an early prognostic factor of metastasis.

[Treatment of breast cancer located behind the nipple with musculocutaneous flap from the latissimus dorsi. 1. Technical aspects]. / Traitement du cancer rétro-aréolaire du sein par lambeau musculo-cutané du grand dorsal. I) Aspects techniques.

The aim of this work is to present a conservative technique of breast retroareolar cancer. After whole excision of nipple areola area, reconstruction is immediately performed by transposition of a myocutaneous latissimus dorsi flap. After local radiotherapy, a new areola and nipple can then be made a few months later.

[Treatment of breast cancer located behind the nipple with musculocutaneous flap from the latissimus dorsi. 2) Analysis of a series of 14 cases]. / Traitement du cancer rétro-aréolaire du sein par lambeau musculo-cutané du grand dorsal. II) Analyse d'une série de 14 cas.

The authors report a series of 14 cases of retroareolar breast cancer treated by wide excision followed by reconstruction with latissimus dorsi flap. Based on clinical and histological datas, they establish surgical indications and show that this procedure can be used for central tumors whose diameter goes from 1.5 to 3 cm even if the nipple is retracted. Cosmetical and functional results are usually goods. They just have to note one infection medically treated.

[The musculocutaneous flap of the latissimus dorsi in the treatment of recurrences of breast cancer]. / Le lambeau musculo-cutané du grand dorsal dans le traitement des récidives de cancer du sein.

Breast cancers local recurrence treatment usually requires a large chirurgical resection. Latissimus dorsi myocutaneous flap was used after mastectomy in 27 patients. This technique was performed in 14 patients who had a recurrence after exclusive radiotherapy treatment. The follow-up of all the patients was more than 5 years. A 42% survival rate has been quoted in this group, after a 11 years period. Latissimus dorsi myocutaneous flap seems to be a satisfactory alternative when performing reconstruction after wall excision under 300 cm2, excepted for recurrence of fast kinetic cancers.

[Immediate use of an expander during mastectomy. Analysis of 120 cases]. / L'utilisation immédiate d'un expanseur lors de la mammectomie. Analyse de 120 cas.

This study analyses a series of 116 patients, in whom mastectomy was followed by immediate insertion of temporary tissue expander. The technique is safe, simple and quick. It carries an acceptably low complication rate. Moreover, it does not interfere with any other local or general adjuvant therapy, if needed. The advantages are rapid post operative healing and psychological recovery, creation of a favorable site for a better quality breast reconstruction. Later on, any procedure for the breast reconstruction can be used. We concluded, that this procedure may be recommended more often; 62% of cases of mastectomies in this series.

Is there an increased incidence of adenomatous polyps in breast cancer patients?

Using flexible proctosigmoidoscopy, the incidence of adenomatous polyps was studied in 161 patients previously operated on for breast cancer and also in 147 hospitalized controls not presenting with colorectal symptoms. The acceptance and tolerance of the examination were good in both populations. The mean age and length of the colons explored were not statistically different for the two groups. The incidence of adenomas was high in the breast cancer group (14.2%) in comparison to the control group (4.7%) (P less than 0.01). This strong incidence especially concerned very small polyps with a diameter smaller than 3 mm. There were also two polyps with superficial carcinomas in the breast cancer group. Breast cancer does indeed seem to represent a condition with a high risk of colorectal adenomas. Our results prompt us to propose the adoption of systematic screening measures and a surveillance schedule as soon as the breast cancer is found.

[Locoregional recurrence of breast cancer. Long-term course of 49 cases treated by excision and omentoplasty]. / Récidives loco-régionales de cancer du sein. Evolution à distance de 49 cas traités par exérèse avec épiplooplastie.

Extensive local recurrence of breast cancer may require wide parietal resection, demanding the use of other tissues to compensate for the loss of substance. We preferably resort to omentoplasty when the defect is larger than 300 cm2. A group of 49 patients with recurrence of the tumor in the breasts (treated with omentoplasty) has been studied, with special emphasis on long-term results. In our series, 86% of the patients were followed up for more than 4 years, with an actuarial survival rate of 46% after 7 years. It thus appears that this procedure can be advocated for slow-developing cancers, the local recurrence of which is extensive and usually isolate for various reasons (most often a deficient initial local treatment).

Role of chemotherapy in acute breast cancer. Analysis of 41 cases.

Clinical and therapeutic results in a series of 41 patients treated for inflammatory cancer of the breast lend emphasis to the selection criteria to be included in a short (approximately two months) clinical history to complement Haagensen's criteria. Chemotherapy improved the previous very poor results obtained in this condition. Survival after surgery and radiotherapy were less than 5% at five years, and this is compared with the prognosis in the series study. However, these results are still only fair in absolute terms and there is still no currently available alternative solution to attempt to achieve a marked improvement in the course of the lesion.

Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene ERBB2.

The expression of the pS2 gene, which is induced by estrogen in the breast cancer cell line MCF-7, has been investigated in breast cancers by using pS2 mRNA determination in tumor specimens and immunocytochemistry to identify pS2 protein in paraffin-embedded sections. Using these assays we show that determination of pS2 gene expression allows the definition of subclasses of estrogen-receptor-containing breast cancers that may be used to more precisely identify estrogen-dependent tumors. Tumor specimens have also been analyzed for the presence of mRNAs for the estrogen receptor and for the ERBB2 oncogene. No evidence for the presence of truncated forms of estrogen-receptor mRNA has been found, and overexpression of the ERBB2 oncogene did not correlate with the steroid receptor status or pS2 gene expression.

[Covering of substantial loss of substance in breast cancer with local complications. Apropos of 57 cases]. / Couverture des grandes pertes de substance en cas de cancer du sein compliqué localement. A propos de 57 cas.

On the basis of 57 cases, the authors report their experience in the repair of substantial losses of tissue caused by surgical resection of local neoplastic recurrences of breast cancers, in particular those situated in irradiated zones, and in certain cases by surgical resection of locally developing and neglected neoplastic lesions. Three types of operation are practised and the techniques involved in these are reviewed: Omentoplasty according to Kiricuta (35 cases), Musculocutaneous flap of the latissimus dorsi muscle (10 cases), Cutaneous and cutaneo-glandular flaps (12 cases). The choice of technique is based on the local conditions and the evolutivity of the neoplastic disease. The results obtained at the local level are then analysed in function of the lesions treated (comparing in particular irradiated and non-irradiated zones), the area resected and the type of operation chosen. Such an analysis reveals that the pedicled omentum flap, owing to its high trophicity, its ease of mobilization and its large size, constitutes the most reliable and effective technique in the treatment of extensive radionecroses. Less substantial losses of tissue may benefit appreciably from the use of a latissimus dorsi musculocutaneous flap, characterized by easy mobilization and high vitality and providing a covering of quality at the cost of a relatively unobtrusive scar. The use of cutaneous flaps can be advocated only for small areas and should be avoided in irradiated zones.