What common biomarkers characterize a triple-negative profile in breast cancer?

Triple-negative breast cancers are not a homogeneous subgroup. There is substantial intra-subgroup diversity in tumor biology, prognosis and treatment sensitivity. Then, these triple-negative phenotype (TNP) groups, having specific features, can be again divided into subclasses based on an added immunohistochemical markers. The challenge in treating TNP breast cancers is that they are not responsive to antiestrogens or trastuzumab secondary to negative receptor status, and as a result have a poor prognosis. Therefore, the presence or absence of supplementary markers could help predict which therapies are best suited for patients based on the pattern that their disease markers show. In this review, we will recapitulate the major supplementary biomarkers related to triple-negative breast cancer, which could give new therapeutic options.

A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.

BACKGROUND: Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer. METHODS: Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP. RESULTS: We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain. CONCLUSIONS: A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history.

Seminal androgens, oestradiol and progesterone in oligoasthenoteratozoospermic men with varicocele.

This study aimed to assess seminal androgens, oestradiol, progesterone levels in oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). In all, 154 men with matched age and body mass index were investigated that were divided into healthy fertile controls (n = 35), OAT men with Vx (n = 55), OAT men without Vx (n = 64). They were subjected to assessment of semen parameters, seminal levels of testosterone (T), androstenedione (A), 5α-androstane-3 α,17 ß-diol (3 α-diol), oestradiol (E2 ), 17-hydroxyprogesterone (17-OHP) and progesterone (P). Seminal levels of T and A were significantly decreased where seminal levels of 3 α-diol, E2 , 17-OHP, P were significantly higher in OAT men with/without Vx compared with fertile controls. Sperm count, sperm motility and sperm normal forms percentage demonstrated significant positive correlation with seminal T and A and significant negative correlation with seminal 3 α-diol, E2 , P. It is concluded that in fertile men, seminal T and A are significantly increased and seminal 3 α-diol, E2 , 17-OHP, P are significantly decreased compared with infertile OAT men with/without Vx. Association of Vx demonstrated a nonsignificant influence on these hormonal levels in OAT cases. Sperm count, sperm motility and sperm normal forms demonstrated significant positive correlation with seminal T, A and significant negative correlation with seminal 3 α-diol, E2 , P.

Biological therapy of strontium-substituted bioglass for soft tissue wound-healing: responses to oxidative stress in ovariectomised rats.

New synthetic biomaterials are constantly being developed for wound repair and regeneration. Bioactive glasses (BG) containing strontium have shown successful applications in tissue engineering account of their biocompatibility and the positive biological effects after implantation. This study aimed to assess whether BG-Sr was accepted by the host tissue and to characterize oxidative stress biomarker and antioxidant enzyme profiles during muscle and skin healing. Wistar rats were divided into five groups (six animals per group): the group (I) was used as negative control (T), after ovariectomy, groups II, III, IV and V were used respectively as positive control (OVX), implanted tissue with BG (OVX-BG), BG-Sr (OVX-BG-Sr) and presented empty defects (OVX-NI). Soft tissues surrounding biomaterials were used to estimate superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) concentration. Our results show that 60 days after operation, treatment of rats with BG-Sr significantly increased MDA concentration and caused an increase of SOD, CAT and GPx activities in both skin and muscular tissues. BG-Sr revealed maturation of myotubes followed a normal appearance of muscle regenerated with high density and mature capillary vessels. High wound recovery with complete re-epithelialization and regeneration of skin was observed. The results demonstrate that the protective action against reactive oxygen species (ROS) was clearly observed in soft tissue surrounding BG-Sr. Moreover, the potential use of BG-Sr rapidly restores the wound skin and muscle structural and functional properties. The BG advantages such as ion release might make BG-Sr an effective biomaterial choice for antioxidative activity.

[Appendicular cystadenocarcinoma with cutaneous fistula]. / Cystadénocarcinome appendiculaire fistulisé à la peau.

BACKGROUND: Cutaneous metastasis of colorectal cancer is rare. We report a case of fistular lesions of the buttocks revealing a mixed tumour of the appendix involving mucinous cystadenocarcinoma and carcinoid tumour. CASE REPORT: A 67-year-old woman was admitted for four skin fistulae of the right buttock present for 6 years. Histological examination of skin biopsy specimens identified infiltration of the dermis by metastatic mucinous adenocarcinoma while colonoscopy showed a caecal tumour measuring 4 cm. Surgical excision was performed involving right hemicolectomy, evacuation of retroperitoneal mucin collection and excision of fistulae. Histopathological examination of surgical specimen confirmed mixed tumour consisting of perforated mucinous cystadenocarcinoma and carcinoid tumour of the appendix. Recurrence of the fistular lesions was seen. The patient was hospitalized several times for surgical drainage of mucin. She died one year later. DISCUSSION: Cutaneous metastasis of colorectal cancer is an uncommon event that usually occurs after identification of the primary tumour and generally indicates advanced-stage disease and an ominous prognosis. This case is particular and underlines the need to rule out a metastatic origin of cutaneous fistulae, even in patients otherwise apparently in good health.

[Recurrent inflammatory myofibroblastic tumor with renal, retroperitoneal and lymph node involvement]. / Tumeur myofibroblastique inflammatoire récurrente avec triple localisation, rénale, rétropéritonéale et ganglionnaire.

Inflammatory myofibroblastic tumors are uncommon and benign tumors with unknown aetiology. First reported in the lungs, the inflammatory myofibroblastic tumors have been observed in other locations, especially in the abdomen and the pelvis. We report a 14-year-old adolescent female, who presented sequentially an inflammatory pseudotumor of lymph node, the left kidney and the retroperitoneum. Extrapulmonary inflammatory myofibroblastic tumors are mesenchymal solid tumors. They are frequently circumscribed and confined to a single organ. The recurrence of some inflammatory myofibroblastic tumors and their expression of chromosomal abnormalities found in some types of lymphoma suggest that some of these lesions constitute a true neoplastic process.

[The solid pseudopapillary tumor of pancreas: two cases and literature review]. / Tumeurs pseudopapillaires et solides du pancréas: deux observations et revue de la littérature.

Solid pseudopapillary tumor (SPT) of the pancreas is a rare exocrine pancreatic tumor behaving in a low-grade fashion, with limited local invasion risk and a rare metastatic evolution. We report SPT in two young females, revealed by abdominal pain and an epigastric mass. The diagnosis of a cystic tumor was based on abdominal ultrasound and CT data in the first case and on MRI in the second. A distal pancreatectomy and splenectomy were successfully performed in the first case and a central pancreatectomy in the second. Histological study confirmed the diagnosis of SPT of the pancreas.

[Choroid plexus carcinoma: a case report]. / Carcinome du plexus choroïde : à propos d'un cas.

OBJECTIVE: Choroid plexus carcinomas are rare and occur more frequently in children than in adults. The differential diagnosis includes choroid plexus papilloma and papillary ependymoma. The prognosis is generally poor. The objective of this paper is to discuss the epidemiological characteristics, diagnosis, treatment, and prognosis of this rare childhood tumor. CASE REPORT: A three-year-old child was hospitalized with a history of partial epilepsy and intracranial hypertension. A computed tomography scan showed an intracranial mass measuring 11cm in diameter, extending to the ventricle system with heterogeneous contrast enhancement. He was urgently operated for loss of consciousness. During the operation, the patient developed an abundant hemorrhage and died. The histopathological examination of the excised tumor identified a choroid plexus carcinoma. CONCLUSION: Choroid plexus carcinomas are rare and treatment is currently controversial. Radical excision is quite difficult and associated with excessive blood loss.

[Amelanotic spitzoid melanoma of the digit: case report]. / Melanome spitzoide achromique du doigt: à propos d'une observation.

BACKGROUND: Melanomas of digit is rare, accounting for 1% of all cutaneous melanomas. We report a new case. AIM: Our purpose is to discuss the clinicopathological characteristics and the difficulties encountred in establishing diagnosis of this rare tumor. OBSERVATION: we report the case of a 25-years-old woman, who consulted for nodular and ulcerated lesion of the right index, located in the external face of the metacarpo-phalangeal joint. The nodule was biopsied and histopathologic exam concluded to spitzoid melanoma. The surgical margins were involved. The patient refused surgical recovery. She consulted 3 years later with axillary lymph nodes. A wide excision of the tumor with lymph node biopsy were made. Histological study concluded to a tumoral residu incompletely excided with lymph node metastases. Amputation of the second digit with dissection of the axillary lymph nodes was made. The surgical margins were tumor free. Lung metastases appeared with a follow up of two months. The patient died early after starting chemotherapy with Deticen. CONCLUSION: In our report, clinical presentation was misleading causing a diagnosis and therapeutic delay. Pathologically, all the histological types of melanoma were described in the digit except spitzoid melanoma.

[Extrafollicular adenomatoid odontogenic tumour: report of two cases]. / Tumeur odontogène adénomatoïde extrafolliculaire: à propos de deux cas.

The purpose of this study was to analysis the clinicopathological features of adenomatoid odontogenic tumour extrafollicular and to discuss the diagnosis pitfull. We present two cases diagnosed and followed at the C.H.U. Habib Bourguiba, Sfax. It is about a 15 year-old boy and a 46 year-old woman who presented gingival swelling. The panoramic radiographs showed in both cases, a radiolucent area affecting teeth 23, 24 and 35 respectively. A computed tomography scan, realized at the second cas, demonstrated an expansile lesion with a sclerotic rim. An exploratory surgical approach was chosen and the final diagnosis was microscopically confirmed to be an extrafollicular variant of adenomatoid odontogenic tumour. The patients were healthy and have not shown any signs of recurrence at follow-up. The two cases described illustrate clinical and radiographic features of the extrafollicular variant of adenomatoid odontogenic tumour. Careful diagnostic procedure and adequate interpretation of radiographic findings may result in a correct diagnosis with otherwise may result in unnecessary endodontic treatment.

[Unusual tumor of the stomach]. / Tumeur inhabituelle de l'estomac.

Stomach melanomas are exceptional and often secondary to cutaneous tumors. Their symptomatology is not specific. We report the case of a 66-year-old woman, hospitalized with a three month history of epigastric pain and weight loss. Gastroscopy had revealed a polyp of the gastric mucosa. Histopathologic examination confirmed the diagnosis of a gastric infiltration by a melanoma. At exploration, there were lung, liver and bone metastasis and no cutaneous melanoma. The diagnosis of polymetastasis from a melanoma without primitive was kept. The patient died three months later.

[Anatomo-clinical features of an erysipeloid form of cutaneous leismaniasis in Tunisia]. / Particularités anatomo-cliniques d'une forme érysipéloïde de leishmaniose cutanée en Tunisie.

The erysipeloid form of cutaneous leishmaniasis is considered as an unusual and rare clinical presentation in Tunisia. Our prospective study on 4 observations, aimed at examining the clinical, histological and progressive features of the "erysipeloid" form of cutaneous leishmaniasis. Our patients were 3 females and one male more than 62 years old. Their cutaneous leishmaniasis was clinically characterised by an infiltrated and extensive plaque which was localised on the face covering the nose and cheeks looking like erysipelas. The treatment was intramuscular meglumine antimoniate (Glucantime) in three cases and metronidazole in one case. A regression without scar was noticed in all the cases. On the histological examination, we observed an intense epidermic and constant hyperplasia with presence of amastigotes in 3 cases. Our study shows the lesional polymorphism of the old word cutaneous leishmaniasis in our region. The "erysipeloid" form of cutaneous leishmaniasis is a rare clinical presentation which generally affects women. If the clinical aspect is very meaningful, the histological aspect is meaningful but not specific.

[Sporotrichoid cutaneous leishmaniasis in Tunisia: a clinical and histological study]. / Forme sporotrichoïde de leishmaniose cutanée en Tunisie: étude clinique et histologique.

BACKGROUND: The sporotrichoid variety of cutaneous leishmaniasis is defined by the presence of dermal and hypodermal nodules along the lymphatic stream, and remote from the primary inoculation lesions. This clinical form is usually considered rare. The aim of our study was to investigate the epidemiological, clinical, histological and evolutionary particularities of sporotrichoid cutaneous leishmaniasis in the south of Tunisia. PATIENTS AND METHODS: During a systematic study of all cases of cutaneous leishmaniasis from the south of Tunisia diagnosed in our hospital in 2002, sporotrichoid forms were diagnosed on the basis of clinical criteria. In all cases of sporotrichoid cutaneous leishmaniasis, the principal clinical characters were systematically specified. Cutaneous biopsies of subcutaneous nodules were performed in six cases. RESULTS: Of 102 patients with cutaneous leishmaniasis, 19 presented sporotrichoid cutaneous leishmaniasis, that is, a frequency of 19%. Between two and 20 painless subcutaneous nodules were arranged in linear strings on the upper leg in 79% of cases. Time to appearance varied between 12 days and one year after the primary lesions. Fourteen appeared without any preliminary treatment for cutaneous leishmaniasis and five appeared after Glucantime infiltration in the primary lesions. Biopsies of the nodules showed an inflammatory infiltrate composed of lymphocytes and histiocytes. This infiltrate was particularly dense and rich in plasmocytes at the level of the deep dermis. The biopsies were deep enough to involve the hypoderm in one case and the same type of infiltrate was noted at the level of interlobular septa. A small number amastigotes was seen in one deep biopsy sample. Outcome was favourable in all cases under treatment. CONCLUSION: Sporotrichoid cutaneous leishmaniasis appears to be common in the south of Tunisia, were cutaneous leishmaniasis is dominant because of Leishmania major. It is not associated with a poor prognosis.

[Head and neck sarcoma]. / Les sarcomes de la tête et du cou.

INTRODUCTION: Head and neck sarcomas comprise a heterogeneous and biologically diverse set of rare neoplasms. The difficulty treating the disease requires multidisciplinary consultation to improve outcome. In an effort to clarify the clinical behavior of head and neck sarcomas and evaluate treatment, we present our experience and review the relevant literature. PATIENTS AND METHODS: This is a retrospective analysis of 15 patients with histologically proven head and neck sarcoma treated in the ENT department between 1998 and 2007. All cases were confirmed by histologic exam with immunohistochemical analysis. RESULTS: Nine women and six men were included in the study. The mean age was 38.4 years (range: 6-73 years). Computed tomography and MRI were done in 66.7% and 60% of the patients, respectively, to evaluate tumor extension. Metastases were demonstrated in three cases. Curative treatment in eight cases was based on different combinations of chemotherapy, radiotherapy, and surgery. Complete remission was obtained in eight cases. Local recurrence was noted in two cases. Two patients died from tumor metastasis. Two patients were lost to follow-up. CONCLUSION: Head and neck sarcomas present diverse rare neoplasms. They make up 5%-20% of all soft tissue sarcomas. All age groups can be affected by this neoplasm, with no predominance in one sex or the other. The most common histologic type is rhabdomyosarcoma, especially in children. Because of the potential for systemic metastasis, extension must be assessed. Treatment is based essentially on the association of surgery, radiotherapy, and chemotherapy to optimize therapeutic results. Five-year survival varies between 44% and 80%.

[Mucinous cystadenoma of the kidney]. / Le cystadénome mucineux du rein.

Mucinous tumors of the kidney are rare. The pathogenesis of these lesions is controversial. We report the observation of a 31-year-old woman presented with right-flank pain and hematuria. Abdominal ultrasonography and computed tomography revealed a multicystic mass of the right kidney. A total nephrectomy was performed. The pathological exam concluded on a mucinous cystadenoma of the right kidney. Mucinous cystadenoma of the kidney with a multicystic presentation has not been previously reported. In this work, we present the different pathogenic hypothesis and the means of treatment of this rare entity.

[Frantz's tumor: anatomoclinical study of six Tunisian cases]. / La tumeur de Frantz: etude anatomoclinique de six cas tunisiens.

Solid and pseudopapillary tumour (Frantz's tumour) is a rare low-grade neoplasm of the pancreas. We report six new cases. Our objective is to specify clinical and pathological characteristics of this rare neoplasm and to discuss its histogenesis. A retrospective review was considered on six Tunisan patients who had solid and pseudopapillary tumor of the pancreas. A review of medical registries and morphological analysis with immunohistochemical study were carried out in all cases. Four patients were female and two patients were male with a median age of 27,5 years (range: 14 - 68 years). Abdominal pain was the most common initial symptoms (5 cases/6). Abdominal computed tomography and/or ultrasonography was used in all the cases. The tumour was in the tail of the pancreas in 4 patients and in the body of the pancreas in one patient; one tumor involved all the pancreas. The median diameter of the tumour was 16,8 cm (range: 8 - 35 cm). Three tumours had an extrapancreatic extension. All patients underwent surgical resection. No adjuvant therapy was recommended. The mean follow up period was 24 months (range: 5 - 78 months). Only one patient died during the surgery. Except for this patient, none experienced tumor recurrence or tumor-related mortality during the follow up period. Solid and pseudopapillary tumour of the pancreas is an uncommon neoplasm which shows distinct clinicopathologically characteristics. Despite diverse studies, its histogenesis remains undetermined. This tumor should be distinguished from other pancreatic neoplasms because its prognosis is excellent after surgical resection.

(AC) dinucleotide repeat polymorphism in intron 1 of human EGFR shows ethnic specificities and high evidence for association with breast cancer.

A polymorphic AC repeat in intron 1 of the EGFR gene was genotyped on 352 healthy individuals and 118 women with breast cancer sampled from the Kuwaiti and Tunisian populations. We compared allele frequencies in these populations with published data on various ethnic groups. We found very close similarity between Tunisian and Kuwaiti populations for both allelic and genotypic frequencies and in both control and patient groups. Our analysis revealed clear interethnic differences between populations; in Europeans, allele 16 occurred predominantly, whereas in Tunisia and Kuwait allele 17 was the most frequent and allele 20 predominated in Asians. One hundred twenty-three healthy women, matched with the 118 breast cancer patients, were used as controls to test for associations between AC repeat and cancer risk. Strong evidence for such an association was found for allele 18 when considered alone (chi2=27.04, corrected p=0.0000016, OR=3.94) or with longer alleles (>17 repeats) (chi2=20.21, p=0.0005, OR=2.30). This contrasts with Asian populations where allele 16 was identified as the risk allele, showing allele heterogeneity depending on ethnicity.

[Expression of c-kit in North African nasopharyngeal carcinomas: correlation with age and LMP1]. / Expression de c-kit dans les carcinomes nasopharyngés nord africains, corrélations avec l'âge et LMP1.

PURPOSE: To determine the level and prognostic significance of c-kit expression in the two age groups of North African nasopharyngeal carcinomas. PATIENTS AND METHODS: A retrospective study of 99 NPC specimens from Tunisian patients was investigated by immunohistochemistry. Immunohistochemical data were correlated with Epstein-Barr virus LMP1 expression and pathological, clinical and survival parameters. RESULTS: c-kit was detected in 79% of the cases for patients under 30 years of age (juvenile form) but in only 56% of specimens in patients over 30 years (P=0.039) and was significantly over-expressed for patients with lymph node involvement (P=0.015). LMP1 score was 5.78 (+/-1.84) for c-kit negative tumors compared to 8,23 (+/-2.39) for c-kit positive tumors (P=0.002). Multivariate analysis including age, lymph nodes involvement and LMP1 expression as co-variables, showed that only age (P=0.027) and LMP1 expression (P=0.005) were significantly correlated to the c-kit expression. CONCLUSION: c-kit is highly expressed in the juvenile form of North African nasopharyngeal carcinomas. There is a significant association between LMP1 and c-kit expression. The contrasted levels of C-kit expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms.

[Mammary hydatid cyst diagnosed by fine needle aspiration]. / Kyste hydatique du sein diagnostiqué par cytoponction.

INTRODUCTION: Echinococcal involvement of the breast is extremely rare and usually not included in the differential diagnosis of breast lumps. OBSERVATION: This is an unreported case of a 56-year-old woman who came with a 3 cm mammary mass. Mammography showed a dense well-circumscribed lesion with calcifications. The diagnosis was established by fine needle aspiration and confirmed by pathological study. CONCLUSION: Hydatid cyst of the breast is rare. The diagnosis by fine needle aspiration is controversial. The treatment is based on complete excision of the cyst.

[Local failures of nasopharynx carcinoma: Anatomoclinical aspects and therapeutic results]. / Aspects anatomocliniques et thérapeutiques des récidives locales des carcinomes du nasopharynx.

PURPOSE: Retrospective analysis of clinical aspects and therapeutic results of nasopharynx cancer local failures. PATIENTS AND METHODS: Forty patients with local failure with or without nodal involvement of nasopharyngeal carcinoma were treated between 1993 and 2013. Reirradiation of nasopharynx was delivered at the dose of 60Gy. Platinum-based chemotherapy was indicated in case of locally advanced disease and/or associated nodal failure. RESULTS: The mean age at diagnosis of primitive tumour was 41.9 years (26-67 years). The mean time of relapse occurrence was 31.7 months (6-104 months). Sixty five percent of failures were confined to the nasopharynx. Nodal failure was seen in 14 cases. Twenty-eight patients had chemotherapy. Twenty-five patients had reirradiation of nasopharynx. Mean follow-up was 98 months (12-191 months). Fourteen patients were still alive and in complete remission. Five-year survival was 40.7%. Xerostomia was the most frequent late toxicity. No haemorrhage was seen. CONCLUSION: Reirradiation is the mainstay treatment of nasopharyngeal local failure. Late toxicity seems to decrease with novel techniques of reirradiation.